Identification

Name
Midostaurin
Accession Number
DB06595
Type
Small Molecule
Groups
Approved
Description

Midostaurin (as Rydapt) is a multitarget kinase inhibitor for the treatment for adult patients with newly diagnosed acute myeloid leukemia (AML) who have a specific genetic mutation called FLT3. It was initially characterized as a potential broad-spectrum antineoplastic agent, with activity toward diverse solid and hematopoietic tumors [4]. It was approved on April 28, 2017 and has shown to increase the overall survival rate in patients with AML as an adjunct therapy along with chemotherapeutic agents.

Structure
Thumb
Synonyms
  • 4'-N-benzoylstaurosporine
External IDs
CGP 41251 / CGP-41251 / NVP-PKC412 / PKC 412 / PKC-412
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
RydaptCapsule, liquid filled25 mg/1OralNovartis2017-04-28Not applicableUs
RydaptCapsule25 mgOralNovartisNot applicableNot applicableCanada
Categories
UNII
ID912S5VON
CAS number
120685-11-2
Weight
Average: 570.649
Monoisotopic: 570.226705462
Chemical Formula
C35H30N4O4
InChI Key
BMGQWWVMWDBQGC-IIFHNQTCSA-N
InChI
InChI=1S/C35H30N4O4/c1-35-32(42-3)25(37(2)34(41)19-11-5-4-6-12-19)17-26(43-35)38-23-15-9-7-13-20(23)28-29-22(18-36-33(29)40)27-21-14-8-10-16-24(21)39(35)31(27)30(28)38/h4-16,25-26,32H,17-18H2,1-3H3,(H,36,40)/t25-,26-,32-,35+/m1/s1
IUPAC Name
N-[(2S,3R,4R,6R)-3-methoxy-2-methyl-16-oxo-29-oxa-1,7,17-triazaoctacyclo[12.12.2.1^{2,6}.0^{7,28}.0^{8,13}.0^{15,19}.0^{20,27}.0^{21,26}]nonacosa-8(13),9,11,14(28),15(19),20(27),21(26),22,24-nonaen-4-yl]-N-methylbenzamide
SMILES
CO[[email protected]@H]1[[email protected]@H](C[[email protected]]2O[[email protected]]1(C)N1C3=C(C=CC=C3)C3=C1C1=C(C4=C(C=CC=C4)N21)C1=C3CNC1=O)N(C)C(=O)C1=CC=CC=C1

Pharmacology

Indication

Investigated for use/treatment in adult patients with high-risk acute myeloid leukemia (AML) who are FLT3 mutation-positive, agressive systemic mastocytosis (ASM), systemic mastocytosis with associated hematological neoplasm (SM-AHN), or mast cell leukemia (MCL).

Structured Indications
Pharmacodynamics

It targets multiple WT and mutated kinases that, when activated, constitutively stimulate aberrant signalling cascades that lead to malignancies such as AML and ASM. Alternative pharmacodynamic effect of midostaurin in prolonging QTc intervals was not clinically significant in patients with advanced SM or AML when compared to placebo. Midostaurin is therapeutically beneficial as a combination therapy for patients undergoing chemotherapy.

Mechanism of action

It potently inhibits multiple receptor tyrosine kinases. Midostaurin and its major active metabolites CGP62221 and CGP52421 inhibit the activity of protein kinase C alpha (PKCalpha), VEGFR2, KIT, PDGFR and WT and/or mutant FLT3 tyrosine kinases. Inhibition of FLT3 receptor signalling cascades induces apoptosis of target leukemia cells expressing target receptors and mast cells, in addition to its antiproliferative activity toward multiple cancer cell lines [4]. Midostaurin also interacts with organic anion transporter (OATP) 1A1 and multidrug resistance protein (MRP)-2 according to preliminary in vitro studies.

TargetActionsOrganism
AProtein kinase C alpha type
antagonist
inhibitor
Human
AVascular endothelial growth factor receptor 2
antagonist
inhibitor
Human
UMast/stem cell growth factor receptor Kit
antagonist
inhibitor
Human
APlatelet-derived growth factor receptor alpha
antagonist
inhibitor
Human
APlatelet-derived growth factor receptor beta
antagonist
inhibitor
Human
AReceptor-type tyrosine-protein kinase FLT3
antagonist
inhibitor
Human
Absorption

The time to reach maximum concentration ranges from 1-3 hrs in fasting patients. The maximum concentration and the time it takes to reach this concentration is reduced up to 20% in presence of a standard meal.

Volume of distribution

The Vd of midostaurin is 95.2L. The parent drug and its main metabolites (CGP62221, CGP52421) are distributed in plasma in vitro.

Protein binding

Midostaurin predominantly binds to α1-acid glycoprotein in vitro. The parent drug and its metabolites are >99.8% bound to plasma proteins in vitro.

Metabolism

Midostaurin is primarily metabolized into CGP62221 and CGP52421 via hepatic CYP3A4 enzymatic activity. The metabolism of CGP62221 takes place initially in a linear relationship whereas CGP52421 formation is an inducible process [5].

Route of elimination

Accounting for 95% of recovered dose eliminated through fecal excretion, 91% was determined as metabolites and 4% as unchanged parent drug. Remaining 5% of the recovered dose is eliminated via renal excretion.

Half life

Elimination half life is approximately 21 hrs for midostaurin, 32 hrs for CGP62221 and 482 hrs for CGP52421.

Clearance

The clearance values of during the initial formation of metabolites are 1.47 L/h for CGP62221 metabolite and 0.501 L/h for CGP52421. 28 days following the oral administration of midostaurin, the clearance of CGP52421 may increase up to 5.2 fold in a recommended dose of 25 mg, resulting in a 2.1- to 2.5-fold increase in total clearance of midostaurin [5].

Toxicity

In a fertility study involving female and male rats, there is evidence of reproductive toxicity including reduced sperm count and decline pregnancy rates when administering 0.01 to 0.1 times the recommended dose in humans. LD50 for oral midostaurin for mouse, rat and rabbit are 300mg/kg, 980mg/kg and 3200mg/kg, respectively [8]. Incidences of pulmonary toxicities including interstitial lung disease and pneumonitis have occured in few patients undergoing midostaurin monotherapy or combination therapy.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
4-MethoxyamphetamineThe metabolism of 4-Methoxyamphetamine can be decreased when combined with Midostaurin.Experimental, Illicit
AbemaciclibThe serum concentration of Abemaciclib can be decreased when it is combined with Midostaurin.Approved
AceclofenacThe metabolism of Aceclofenac can be decreased when combined with Midostaurin.Approved, Investigational
AcenocoumarolThe metabolism of Acenocoumarol can be decreased when combined with Midostaurin.Approved
AcetaminophenThe metabolism of Acetaminophen can be decreased when combined with Midostaurin.Approved
AcetylcholineThe metabolism of Acetylcholine can be decreased when combined with Midostaurin.Approved
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Midostaurin.Approved
AcetyldigoxinAcetyldigoxin may decrease the cardiotoxic activities of Midostaurin.Experimental
Acetylsalicylic acidThe metabolism of Acetylsalicylic acid can be decreased when combined with Midostaurin.Approved, Vet Approved
AgomelatineThe serum concentration of Agomelatine can be increased when it is combined with Midostaurin.Approved, Investigational
AjmalineThe metabolism of Ajmaline can be decreased when combined with Midostaurin.Approved, Investigational
AlbendazoleThe metabolism of Albendazole can be decreased when combined with Midostaurin.Approved, Vet Approved
AlmotriptanThe metabolism of Almotriptan can be decreased when combined with Midostaurin.Approved, Investigational
AlogliptinThe metabolism of Alogliptin can be decreased when combined with Midostaurin.Approved
AlosetronThe metabolism of Alosetron can be decreased when combined with Midostaurin.Approved, Withdrawn
AlprazolamThe metabolism of Alprazolam can be decreased when combined with Midostaurin.Approved, Illicit, Investigational
AlprenololThe metabolism of Alprenolol can be decreased when combined with Midostaurin.Approved, Withdrawn
AminophenazoneThe metabolism of Aminophenazone can be decreased when combined with Midostaurin.Approved, Withdrawn
AminophyllineThe metabolism of Aminophylline can be decreased when combined with Midostaurin.Approved
AmiodaroneThe metabolism of Midostaurin can be decreased when combined with Amiodarone.Approved, Investigational
AmitriptylineThe metabolism of Amitriptyline can be decreased when combined with Midostaurin.Approved
AmodiaquineThe serum concentration of Amodiaquine can be increased when it is combined with Midostaurin.Approved, Investigational
AmoxapineThe metabolism of Amoxapine can be decreased when combined with Midostaurin.Approved
AmphetamineThe metabolism of Amphetamine can be decreased when combined with Midostaurin.Approved, Illicit
AmprenavirThe metabolism of Amprenavir can be decreased when combined with Midostaurin.Approved
AmsacrineThe metabolism of Amsacrine can be decreased when combined with Midostaurin.Approved
AnagrelideThe metabolism of Anagrelide can be decreased when combined with Midostaurin.Approved
AntipyrineThe metabolism of Antipyrine can be decreased when combined with Midostaurin.Approved
ApixabanThe metabolism of Apixaban can be decreased when combined with Midostaurin.Approved
AprepitantThe serum concentration of Midostaurin can be increased when it is combined with Aprepitant.Approved, Investigational
AprindineThe metabolism of Aprindine can be decreased when combined with Midostaurin.Approved
Arachidonic AcidThe metabolism of Arachidonic Acid can be decreased when combined with Midostaurin.Experimental
ArformoterolThe metabolism of Arformoterol can be decreased when combined with Midostaurin.Approved, Investigational
AripiprazoleThe serum concentration of Aripiprazole can be increased when it is combined with Midostaurin.Approved, Investigational
ArtemetherThe metabolism of Artemether can be decreased when combined with Midostaurin.Approved
AsenapineThe metabolism of Asenapine can be decreased when combined with Midostaurin.Approved
AstemizoleThe metabolism of Astemizole can be decreased when combined with Midostaurin.Approved, Withdrawn
AtazanavirThe metabolism of Midostaurin can be decreased when combined with Atazanavir.Approved, Investigational
AtomoxetineThe serum concentration of Atomoxetine can be increased when it is combined with Midostaurin.Approved
AV650The metabolism of AV650 can be decreased when combined with Midostaurin.Approved, Investigational
AxitinibThe metabolism of Axitinib can be decreased when combined with Midostaurin.Approved, Investigational
AzelastineThe metabolism of Azelastine can be decreased when combined with Midostaurin.Approved
BendamustineThe serum concentration of Bendamustine can be increased when it is combined with Midostaurin.Approved, Investigational
BenzatropineThe metabolism of Benzatropine can be decreased when combined with Midostaurin.Approved
Benzyl alcoholThe metabolism of Benzyl alcohol can be decreased when combined with Midostaurin.Approved
BepridilThe metabolism of Bepridil can be decreased when combined with Midostaurin.Approved, Withdrawn
BetaxololThe metabolism of Betaxolol can be decreased when combined with Midostaurin.Approved
BevacizumabBevacizumab may increase the cardiotoxic activities of Midostaurin.Approved, Investigational
BexaroteneThe metabolism of Bexarotene can be decreased when combined with Midostaurin.Approved, Investigational
BisoprololThe metabolism of Bisoprolol can be decreased when combined with Midostaurin.Approved
BoceprevirThe metabolism of Midostaurin can be decreased when combined with Boceprevir.Approved, Withdrawn
BortezomibThe metabolism of Bortezomib can be decreased when combined with Midostaurin.Approved, Investigational
BosentanThe serum concentration of Bosentan can be increased when it is combined with Midostaurin.Approved, Investigational
BrexpiprazoleThe serum concentration of Brexpiprazole can be increased when it is combined with Midostaurin.Approved
BrivaracetamThe metabolism of Brivaracetam can be decreased when combined with Midostaurin.Approved, Investigational
BromazepamThe metabolism of Bromazepam can be decreased when combined with Midostaurin.Approved, Illicit
BrompheniramineThe metabolism of Brompheniramine can be decreased when combined with Midostaurin.Approved
BufuralolThe metabolism of Bufuralol can be decreased when combined with Midostaurin.Experimental, Investigational
BupivacaineThe metabolism of Bupivacaine can be decreased when combined with Midostaurin.Approved, Investigational
BuprenorphineThe metabolism of Buprenorphine can be decreased when combined with Midostaurin.Approved, Illicit, Investigational, Vet Approved
BupropionThe metabolism of Bupropion can be decreased when combined with Midostaurin.Approved
BuspironeThe metabolism of Buspirone can be decreased when combined with Midostaurin.Approved, Investigational
CabazitaxelThe risk or severity of adverse effects can be increased when Cabazitaxel is combined with Midostaurin.Approved
CabozantinibThe metabolism of Cabozantinib can be decreased when combined with Midostaurin.Approved
CaffeineThe metabolism of Caffeine can be decreased when combined with Midostaurin.Approved
CandesartanThe metabolism of Candesartan can be decreased when combined with Midostaurin.Experimental
Candesartan cilexetilThe metabolism of Candesartan cilexetil can be decreased when combined with Midostaurin.Approved
CaptoprilThe metabolism of Captopril can be decreased when combined with Midostaurin.Approved
CarbamazepineThe metabolism of Midostaurin can be increased when combined with Carbamazepine.Approved, Investigational
CarbinoxamineThe metabolism of Carbinoxamine can be decreased when combined with Midostaurin.Approved
CariprazineThe metabolism of Cariprazine can be decreased when combined with Midostaurin.Approved
CarmustineThe metabolism of Carmustine can be decreased when combined with Midostaurin.Approved
CarteololThe metabolism of Carteolol can be decreased when combined with Midostaurin.Approved
CarvedilolThe serum concentration of Carvedilol can be increased when it is combined with Midostaurin.Approved, Investigational
CelecoxibThe metabolism of Celecoxib can be decreased when combined with Midostaurin.Approved, Investigational
CephalexinThe metabolism of Cephalexin can be decreased when combined with Midostaurin.Approved, Vet Approved
CeritinibThe serum concentration of Midostaurin can be increased when it is combined with Ceritinib.Approved
CevimelineThe metabolism of Cevimeline can be decreased when combined with Midostaurin.Approved
ChlordiazepoxideThe metabolism of Chlordiazepoxide can be decreased when combined with Midostaurin.Approved, Illicit
ChloroquineThe metabolism of Chloroquine can be decreased when combined with Midostaurin.Approved, Vet Approved
ChlorphenamineThe metabolism of Chlorphenamine can be decreased when combined with Midostaurin.Approved
ChlorpromazineThe metabolism of Chlorpromazine can be decreased when combined with Midostaurin.Approved, Vet Approved
ChlorpropamideThe metabolism of Chlorpropamide can be decreased when combined with Midostaurin.Approved
ChlorzoxazoneThe metabolism of Chlorzoxazone can be decreased when combined with Midostaurin.Approved
CilostazolThe serum concentration of Cilostazol can be increased when it is combined with Midostaurin.Approved
CinacalcetThe metabolism of Cinacalcet can be decreased when combined with Midostaurin.Approved
CinnarizineThe metabolism of Cinnarizine can be decreased when combined with Midostaurin.Approved, Investigational
CisaprideThe metabolism of Cisapride can be decreased when combined with Midostaurin.Approved, Investigational, Withdrawn
CitalopramThe metabolism of Citalopram can be decreased when combined with Midostaurin.Approved
ClarithromycinThe metabolism of Midostaurin can be decreased when combined with Clarithromycin.Approved
ClemastineThe metabolism of Midostaurin can be decreased when combined with Clemastine.Approved
ClenbuterolThe metabolism of Clenbuterol can be decreased when combined with Midostaurin.Approved, Investigational, Vet Approved
ClevidipineThe metabolism of Clevidipine can be decreased when combined with Midostaurin.Approved
ClomipramineThe metabolism of Clomipramine can be decreased when combined with Midostaurin.Approved, Vet Approved
ClonidineThe metabolism of Clonidine can be decreased when combined with Midostaurin.Approved
ClopidogrelThe metabolism of Clopidogrel can be decreased when combined with Midostaurin.Approved, Nutraceutical
ClotrimazoleThe metabolism of Midostaurin can be decreased when combined with Clotrimazole.Approved, Vet Approved
ClozapineThe serum concentration of Clozapine can be increased when it is combined with Midostaurin.Approved
CobicistatThe metabolism of Midostaurin can be decreased when combined with Cobicistat.Approved
CodeineThe therapeutic efficacy of Codeine can be decreased when used in combination with Midostaurin.Approved, Illicit
ConivaptanThe serum concentration of Midostaurin can be increased when it is combined with Conivaptan.Approved, Investigational
Conjugated estrogensThe metabolism of Conjugated estrogens can be decreased when combined with Midostaurin.Approved
CrizotinibThe metabolism of Midostaurin can be decreased when combined with Crizotinib.Approved
CyclobenzaprineThe metabolism of Cyclobenzaprine can be decreased when combined with Midostaurin.Approved
CyclophosphamideCyclophosphamide may increase the cardiotoxic activities of Midostaurin.Approved, Investigational
CyclosporineThe metabolism of Midostaurin can be decreased when combined with Cyclosporine.Approved, Investigational, Vet Approved
CymarinCymarin may decrease the cardiotoxic activities of Midostaurin.Experimental
DabrafenibThe serum concentration of Midostaurin can be decreased when it is combined with Dabrafenib.Approved
DacarbazineThe metabolism of Dacarbazine can be decreased when combined with Midostaurin.Approved, Investigational
DapagliflozinThe metabolism of Dapagliflozin can be decreased when combined with Midostaurin.Approved
DapsoneThe metabolism of Dapsone can be decreased when combined with Midostaurin.Approved, Investigational
DarifenacinThe metabolism of Darifenacin can be decreased when combined with Midostaurin.Approved, Investigational
DarunavirThe metabolism of Midostaurin can be decreased when combined with Darunavir.Approved
DasabuvirThe metabolism of Dasabuvir can be decreased when combined with Midostaurin.Approved
DasatinibThe serum concentration of Midostaurin can be increased when it is combined with Dasatinib.Approved, Investigational
DaunorubicinThe metabolism of Daunorubicin can be decreased when combined with Midostaurin.Approved
DebrisoquinThe metabolism of Debrisoquin can be decreased when combined with Midostaurin.Approved, Investigational
DeferasiroxThe serum concentration of Midostaurin can be decreased when it is combined with Deferasirox.Approved, Investigational
DelavirdineThe metabolism of Delavirdine can be decreased when combined with Midostaurin.Approved
DesipramineThe metabolism of Desipramine can be decreased when combined with Midostaurin.Approved
DeslanosideDeslanoside may decrease the cardiotoxic activities of Midostaurin.Approved
DeutetrabenazineThe metabolism of Deutetrabenazine can be decreased when combined with Midostaurin.Approved, Investigational
Dexchlorpheniramine maleateThe metabolism of Dexchlorpheniramine maleate can be decreased when combined with Midostaurin.Approved
DexfenfluramineThe metabolism of Dexfenfluramine can be decreased when combined with Midostaurin.Approved, Illicit, Investigational, Withdrawn
DexmethylphenidateThe metabolism of Dexmethylphenidate can be decreased when combined with Midostaurin.Approved
DextroamphetamineThe metabolism of Dextroamphetamine can be decreased when combined with Midostaurin.Approved, Illicit
DextromethorphanThe metabolism of Dextromethorphan can be decreased when combined with Midostaurin.Approved
DiazepamThe metabolism of Diazepam can be decreased when combined with Midostaurin.Approved, Illicit, Vet Approved
DiclofenacThe serum concentration of Diclofenac can be increased when it is combined with Midostaurin.Approved, Vet Approved
DicoumarolThe metabolism of Dicoumarol can be decreased when combined with Midostaurin.Approved
DigitoxinDigitoxin may decrease the cardiotoxic activities of Midostaurin.Approved, Investigational
DigoxinDigoxin may decrease the cardiotoxic activities of Midostaurin.Approved
Digoxin Immune Fab (Ovine)Digoxin Immune Fab (Ovine) may decrease the cardiotoxic activities of Midostaurin.Approved
DihydrocodeineThe metabolism of Dihydrocodeine can be decreased when combined with Midostaurin.Approved, Illicit
DihydroergotamineThe metabolism of Midostaurin can be decreased when combined with Dihydroergotamine.Approved
DiltiazemThe metabolism of Diltiazem can be decreased when combined with Midostaurin.Approved
DinoprostoneThe metabolism of Dinoprostone can be decreased when combined with Midostaurin.Approved
DiphenhydramineThe metabolism of Diphenhydramine can be decreased when combined with Midostaurin.Approved
DocetaxelThe risk or severity of adverse effects can be increased when Docetaxel is combined with Midostaurin.Approved, Investigational
DoconexentThe metabolism of Doconexent can be decreased when combined with Midostaurin.Approved, Investigational
DolasetronThe metabolism of Dolasetron can be decreased when combined with Midostaurin.Approved
DomperidoneThe metabolism of Domperidone can be decreased when combined with Midostaurin.Approved, Investigational, Vet Approved
DonepezilThe metabolism of Donepezil can be decreased when combined with Midostaurin.Approved
DopamineThe metabolism of Dopamine can be decreased when combined with Midostaurin.Approved
DorzolamideThe metabolism of Dorzolamide can be decreased when combined with Midostaurin.Approved
DoxazosinThe metabolism of Doxazosin can be decreased when combined with Midostaurin.Approved
DoxepinThe metabolism of Doxepin can be decreased when combined with Midostaurin.Approved
DoxorubicinThe serum concentration of Doxorubicin can be increased when it is combined with Midostaurin.Approved, Investigational
DoxorubicinThe metabolism of Doxorubicin can be decreased when combined with Midostaurin.Approved, Investigational
DoxycyclineThe metabolism of Midostaurin can be decreased when combined with Doxycycline.Approved, Investigational, Vet Approved
DronabinolThe serum concentration of Dronabinol can be increased when it is combined with Midostaurin.Approved, Illicit
DronedaroneThe metabolism of Dronedarone can be decreased when combined with Midostaurin.Approved
DuloxetineThe serum concentration of Duloxetine can be increased when it is combined with Midostaurin.Approved
EletriptanThe metabolism of Eletriptan can be decreased when combined with Midostaurin.Approved, Investigational
EliglustatThe serum concentration of Eliglustat can be increased when it is combined with Midostaurin.Approved
EltrombopagThe metabolism of Eltrombopag can be decreased when combined with Midostaurin.Approved
EnasidenibThe metabolism of Enasidenib can be decreased when combined with Midostaurin.Approved
EncainideThe metabolism of Encainide can be decreased when combined with Midostaurin.Approved, Investigational, Withdrawn
EnclomipheneThe metabolism of Enclomiphene can be decreased when combined with Midostaurin.Investigational
EnzalutamideThe serum concentration of Midostaurin can be decreased when it is combined with Enzalutamide.Approved
EpinastineThe metabolism of Epinastine can be decreased when combined with Midostaurin.Approved, Investigational
EpoprostenolThe metabolism of Epoprostenol can be decreased when combined with Midostaurin.Approved
ErgotamineThe metabolism of Ergotamine can be decreased when combined with Midostaurin.Approved
ErlotinibThe metabolism of Erlotinib can be decreased when combined with Midostaurin.Approved, Investigational
ErythromycinThe metabolism of Midostaurin can be decreased when combined with Erythromycin.Approved, Vet Approved
EscitalopramThe metabolism of Escitalopram can be decreased when combined with Midostaurin.Approved, Investigational
EsmirtazapineThe metabolism of Esmirtazapine can be decreased when combined with Midostaurin.Investigational
EstradiolThe metabolism of Estradiol can be decreased when combined with Midostaurin.Approved, Investigational, Vet Approved
EstroneThe metabolism of Estrone can be decreased when combined with Midostaurin.Approved
Estrone sulfateThe metabolism of Estrone sulfate can be decreased when combined with Midostaurin.Approved
EszopicloneThe metabolism of Eszopiclone can be decreased when combined with Midostaurin.Approved
EthanolThe metabolism of Ethanol can be decreased when combined with Midostaurin.Approved
EthylmorphineThe metabolism of Ethylmorphine can be decreased when combined with Midostaurin.Approved, Illicit
EtodolacThe metabolism of Etodolac can be decreased when combined with Midostaurin.Approved, Investigational, Vet Approved
EtoposideThe metabolism of Etoposide can be decreased when combined with Midostaurin.Approved
EtoricoxibThe metabolism of Etoricoxib can be decreased when combined with Midostaurin.Approved, Investigational
EtravirineThe metabolism of Etravirine can be decreased when combined with Midostaurin.Approved
FesoterodineThe serum concentration of the active metabolites of Fesoterodine can be increased when Fesoterodine is used in combination with Midostaurin.Approved
FingolimodThe metabolism of Fingolimod can be decreased when combined with Midostaurin.Approved, Investigational
FlecainideThe metabolism of Flecainide can be decreased when combined with Midostaurin.Approved, Withdrawn
FluconazoleThe metabolism of Midostaurin can be decreased when combined with Fluconazole.Approved
FlunarizineThe metabolism of Flunarizine can be decreased when combined with Midostaurin.Approved
FlunitrazepamThe metabolism of Flunitrazepam can be decreased when combined with Midostaurin.Approved, Illicit
FluorouracilThe metabolism of Fluorouracil can be decreased when combined with Midostaurin.Approved
FluoxetineThe metabolism of Fluoxetine can be decreased when combined with Midostaurin.Approved, Vet Approved
FluphenazineThe metabolism of Fluphenazine can be decreased when combined with Midostaurin.Approved
FlurbiprofenThe metabolism of Flurbiprofen can be decreased when combined with Midostaurin.Approved, Investigational
FlutamideThe metabolism of Flutamide can be decreased when combined with Midostaurin.Approved
FluvastatinThe metabolism of Fluvastatin can be decreased when combined with Midostaurin.Approved
FluvoxamineThe metabolism of Fluvoxamine can be decreased when combined with Midostaurin.Approved, Investigational
FormoterolThe metabolism of Formoterol can be decreased when combined with Midostaurin.Approved, Investigational
FosamprenavirThe metabolism of Midostaurin can be decreased when combined with Fosamprenavir.Approved
FosaprepitantThe serum concentration of Midostaurin can be increased when it is combined with Fosaprepitant.Approved
FosphenytoinThe metabolism of Midostaurin can be increased when combined with Fosphenytoin.Approved
FrovatriptanThe metabolism of Frovatriptan can be decreased when combined with Midostaurin.Approved, Investigational
Fusidic AcidThe serum concentration of Midostaurin can be increased when it is combined with Fusidic Acid.Approved
GalantamineThe metabolism of Galantamine can be decreased when combined with Midostaurin.Approved
GavestinelThe metabolism of Gavestinel can be decreased when combined with Midostaurin.Investigational
GefitinibThe metabolism of Gefitinib can be decreased when combined with Midostaurin.Approved, Investigational
GenisteinThe metabolism of Genistein can be decreased when combined with Midostaurin.Investigational
GitoformateGitoformate may decrease the cardiotoxic activities of Midostaurin.Experimental
GliclazideThe metabolism of Gliclazide can be decreased when combined with Midostaurin.Approved
GlimepirideThe metabolism of Glimepiride can be decreased when combined with Midostaurin.Approved
GlipizideThe metabolism of Glipizide can be decreased when combined with Midostaurin.Approved
GlyburideThe metabolism of Glyburide can be decreased when combined with Midostaurin.Approved
GranisetronThe metabolism of Granisetron can be decreased when combined with Midostaurin.Approved, Investigational
GrepafloxacinThe metabolism of Grepafloxacin can be decreased when combined with Midostaurin.Investigational, Withdrawn
GuanabenzThe metabolism of Guanabenz can be decreased when combined with Midostaurin.Approved, Investigational
GuanfacineThe metabolism of Guanfacine can be decreased when combined with Midostaurin.Approved, Investigational
HalofantrineThe metabolism of Halofantrine can be decreased when combined with Midostaurin.Approved
HaloperidolThe metabolism of Haloperidol can be decreased when combined with Midostaurin.Approved
HalothaneThe metabolism of Halothane can be decreased when combined with Midostaurin.Approved, Vet Approved
HesperetinThe metabolism of Hesperetin can be decreased when combined with Midostaurin.Approved
HexobarbitalThe metabolism of Hexobarbital can be decreased when combined with Midostaurin.Approved
HistamineThe metabolism of Histamine can be decreased when combined with Midostaurin.Approved, Investigational
HydrocodoneThe serum concentration of the active metabolites of Hydrocodone can be reduced when Hydrocodone is used in combination with Midostaurin resulting in a loss in efficacy.Approved, Illicit
HydromorphoneThe metabolism of Hydromorphone can be decreased when combined with Midostaurin.Approved, Illicit
IbrutinibThe metabolism of Ibrutinib can be decreased when combined with Midostaurin.Approved
IbuprofenThe metabolism of Ibuprofen can be decreased when combined with Midostaurin.Approved
IcotinibThe metabolism of Icotinib can be decreased when combined with Midostaurin.Approved, Investigational
IdarubicinThe metabolism of Idarubicin can be decreased when combined with Midostaurin.Approved
IdelalisibThe serum concentration of Midostaurin can be increased when it is combined with Idelalisib.Approved
IfosfamideThe metabolism of Ifosfamide can be decreased when combined with Midostaurin.Approved
IloperidoneThe serum concentration of the active metabolites of Iloperidone can be increased when Iloperidone is used in combination with Midostaurin.Approved
ImatinibThe metabolism of Imatinib can be decreased when combined with Midostaurin.Approved
ImipramineThe metabolism of Imipramine can be decreased when combined with Midostaurin.Approved
ImiquimodThe metabolism of Imiquimod can be decreased when combined with Midostaurin.Approved, Investigational
IndinavirThe metabolism of Midostaurin can be decreased when combined with Indinavir.Approved
indisulamThe metabolism of indisulam can be decreased when combined with Midostaurin.Investigational
IndomethacinThe metabolism of Indomethacin can be decreased when combined with Midostaurin.Approved, Investigational
Ipratropium bromideThe metabolism of Ipratropium bromide can be decreased when combined with Midostaurin.Approved
IrbesartanThe metabolism of Irbesartan can be decreased when combined with Midostaurin.Approved, Investigational
IsavuconazoniumThe metabolism of Midostaurin can be decreased when combined with Isavuconazonium.Approved, Investigational
IsradipineThe metabolism of Midostaurin can be decreased when combined with Isradipine.Approved
ItraconazoleThe metabolism of Midostaurin can be decreased when combined with Itraconazole.Approved, Investigational
IvacaftorThe serum concentration of Midostaurin can be increased when it is combined with Ivacaftor.Approved
IxazomibThe metabolism of Ixazomib can be decreased when combined with Midostaurin.Approved
KetamineThe metabolism of Ketamine can be decreased when combined with Midostaurin.Approved, Vet Approved
KetobemidoneThe metabolism of Ketobemidone can be decreased when combined with Midostaurin.Approved, Investigational
KetoconazoleThe metabolism of Midostaurin can be decreased when combined with Ketoconazole.Approved, Investigational
KetoprofenThe metabolism of Ketoprofen can be decreased when combined with Midostaurin.Approved, Vet Approved
LabetalolThe metabolism of Labetalol can be decreased when combined with Midostaurin.Approved
LacosamideThe serum concentration of Lacosamide can be increased when it is combined with Midostaurin.Approved
Lanatoside CLanatoside C may decrease the cardiotoxic activities of Midostaurin.Experimental
LansoprazoleThe metabolism of Lansoprazole can be decreased when combined with Midostaurin.Approved, Investigational
LeflunomideThe metabolism of Leflunomide can be decreased when combined with Midostaurin.Approved, Investigational
LesinuradThe metabolism of Lesinurad can be decreased when combined with Midostaurin.Approved
LetermovirThe metabolism of Letermovir can be decreased when combined with Midostaurin.Approved
LevobupivacaineThe metabolism of Levobupivacaine can be decreased when combined with Midostaurin.Approved, Investigational
LevodopaThe metabolism of Levodopa can be decreased when combined with Midostaurin.Approved
LevomilnacipranThe metabolism of Levomilnacipran can be decreased when combined with Midostaurin.Approved
LicofeloneThe metabolism of Licofelone can be decreased when combined with Midostaurin.Investigational
LidocaineThe metabolism of Lidocaine can be decreased when combined with Midostaurin.Approved, Vet Approved
LisurideThe metabolism of Lisuride can be decreased when combined with Midostaurin.Approved, Investigational
LomefloxacinThe metabolism of Lomefloxacin can be decreased when combined with Midostaurin.Approved, Investigational
LomustineThe metabolism of Lomustine can be decreased when combined with Midostaurin.Approved
LoperamideThe metabolism of Loperamide can be decreased when combined with Midostaurin.Approved
LopinavirThe metabolism of Midostaurin can be decreased when combined with Lopinavir.Approved
LoratadineThe metabolism of Loratadine can be decreased when combined with Midostaurin.Approved
LorcaserinThe metabolism of Lorcaserin can be decreased when combined with Midostaurin.Approved
LornoxicamThe metabolism of Lornoxicam can be decreased when combined with Midostaurin.Approved, Investigational
LosartanThe metabolism of Losartan can be decreased when combined with Midostaurin.Approved
LovastatinThe metabolism of Midostaurin can be decreased when combined with Lovastatin.Approved, Investigational
LuliconazoleThe serum concentration of Midostaurin can be increased when it is combined with Luliconazole.Approved
LumacaftorThe metabolism of Midostaurin can be increased when combined with Lumacaftor.Approved
LumiracoxibThe metabolism of Lumiracoxib can be decreased when combined with Midostaurin.Approved, Investigational
MalathionThe metabolism of Malathion can be decreased when combined with Midostaurin.Approved, Investigational
MaprotilineThe metabolism of Maprotiline can be decreased when combined with Midostaurin.Approved
Mefenamic acidThe metabolism of Mefenamic acid can be decreased when combined with Midostaurin.Approved
MelatoninThe metabolism of Melatonin can be decreased when combined with Midostaurin.Approved, Nutraceutical, Vet Approved
MeloxicamThe metabolism of Meloxicam can be decreased when combined with Midostaurin.Approved, Vet Approved
MenadioneThe metabolism of Menadione can be decreased when combined with Midostaurin.Approved, Nutraceutical
MephenytoinThe metabolism of Mephenytoin can be decreased when combined with Midostaurin.Investigational, Withdrawn
MequitazineThe serum concentration of Mequitazine can be increased when it is combined with Midostaurin.Approved
MesoridazineThe metabolism of Mesoridazine can be decreased when combined with Midostaurin.Approved, Investigational
MestranolThe metabolism of Mestranol can be decreased when combined with Midostaurin.Approved
MethadoneThe metabolism of Methadone can be decreased when combined with Midostaurin.Approved
MethamphetamineThe metabolism of Methamphetamine can be decreased when combined with Midostaurin.Approved, Illicit
MethotrimeprazineThe metabolism of Methotrimeprazine can be decreased when combined with Midostaurin.Approved
MethoxyfluraneThe metabolism of Methoxyflurane can be decreased when combined with Midostaurin.Approved, Investigational, Vet Approved
MethylphenidateThe metabolism of Methylphenidate can be decreased when combined with Midostaurin.Approved, Investigational
MethyprylonThe metabolism of Methyprylon can be decreased when combined with Midostaurin.Approved, Illicit, Withdrawn
MetildigoxinMetildigoxin may decrease the cardiotoxic activities of Midostaurin.Experimental
MetoclopramideThe metabolism of Metoclopramide can be decreased when combined with Midostaurin.Approved, Investigational
MetoprololThe serum concentration of Metoprolol can be increased when it is combined with Midostaurin.Approved, Investigational
MetronidazoleThe metabolism of Metronidazole can be decreased when combined with Midostaurin.Approved
MexiletineThe metabolism of Mexiletine can be decreased when combined with Midostaurin.Approved
MianserinThe metabolism of Mianserin can be decreased when combined with Midostaurin.Approved, Investigational
MifepristoneThe serum concentration of Midostaurin can be increased when it is combined with Mifepristone.Approved, Investigational
MinaprineThe metabolism of Minaprine can be decreased when combined with Midostaurin.Approved
MirabegronThe metabolism of Mirabegron can be decreased when combined with Midostaurin.Approved
MirtazapineThe metabolism of Mirtazapine can be decreased when combined with Midostaurin.Approved
MitotaneThe serum concentration of Midostaurin can be decreased when it is combined with Mitotane.Approved
MoclobemideThe metabolism of Moclobemide can be decreased when combined with Midostaurin.Approved
MontelukastThe metabolism of Montelukast can be decreased when combined with Midostaurin.Approved
MorphineThe metabolism of Morphine can be decreased when combined with Midostaurin.Approved, Investigational
muraglitazarThe metabolism of muraglitazar can be decreased when combined with Midostaurin.Investigational
NabumetoneThe metabolism of Nabumetone can be decreased when combined with Midostaurin.Approved
NaproxenThe metabolism of Naproxen can be decreased when combined with Midostaurin.Approved, Vet Approved
NateglinideThe metabolism of Nateglinide can be decreased when combined with Midostaurin.Approved, Investigational
NebivololThe serum concentration of Nebivolol can be increased when it is combined with Midostaurin.Approved, Investigational
NefazodoneThe metabolism of Midostaurin can be decreased when combined with Nefazodone.Approved, Withdrawn
NelfinavirThe metabolism of Midostaurin can be decreased when combined with Nelfinavir.Approved
NetupitantThe serum concentration of Midostaurin can be increased when it is combined with Netupitant.Approved
NevirapineThe metabolism of Midostaurin can be increased when combined with Nevirapine.Approved
NicardipineThe metabolism of Nicardipine can be decreased when combined with Midostaurin.Approved
NicergolineThe metabolism of Nicergoline can be decreased when combined with Midostaurin.Approved, Investigational
NiclosamideThe metabolism of Niclosamide can be decreased when combined with Midostaurin.Approved, Investigational, Vet Approved
NicotineThe metabolism of Nicotine can be decreased when combined with Midostaurin.Approved
NifedipineThe metabolism of Nifedipine can be decreased when combined with Midostaurin.Approved
NilotinibThe metabolism of Midostaurin can be decreased when combined with Nilotinib.Approved, Investigational
Nitric OxideThe metabolism of Nitric Oxide can be decreased when combined with Midostaurin.Approved
NitrofuralThe metabolism of Nitrofural can be decreased when combined with Midostaurin.Approved, Investigational, Vet Approved
NortriptylineThe metabolism of Nortriptyline can be decreased when combined with Midostaurin.Approved
OlanzapineThe metabolism of Olanzapine can be decreased when combined with Midostaurin.Approved, Investigational
OlaparibThe metabolism of Midostaurin can be decreased when combined with Olaparib.Approved
OleandrinOleandrin may decrease the cardiotoxic activities of Midostaurin.Experimental, Investigational
OlodaterolThe metabolism of Olodaterol can be decreased when combined with Midostaurin.Approved
OmeprazoleThe metabolism of Omeprazole can be decreased when combined with Midostaurin.Approved, Investigational, Vet Approved
OndansetronThe metabolism of Ondansetron can be decreased when combined with Midostaurin.Approved
OsimertinibThe serum concentration of Midostaurin can be increased when it is combined with Osimertinib.Approved
OspemifeneThe serum concentration of Ospemifene can be increased when it is combined with Midostaurin.Approved
OuabainOuabain may decrease the cardiotoxic activities of Midostaurin.Approved
OxaliplatinThe metabolism of Oxaliplatin can be decreased when combined with Midostaurin.Approved, Investigational
OxaprozinThe metabolism of Oxaprozin can be decreased when combined with Midostaurin.Approved
OxtriphyllineThe metabolism of Oxtriphylline can be decreased when combined with Midostaurin.Approved
OxycodoneThe metabolism of Oxycodone can be decreased when combined with Midostaurin.Approved, Illicit, Investigational
OxymorphoneThe metabolism of Oxymorphone can be decreased when combined with Midostaurin.Approved, Investigational, Vet Approved
PaclitaxelThe risk or severity of adverse effects can be increased when Paclitaxel is combined with Midostaurin.Approved, Vet Approved
PalbociclibThe serum concentration of Midostaurin can be increased when it is combined with Palbociclib.Approved
PalonosetronThe metabolism of Palonosetron can be decreased when combined with Midostaurin.Approved, Investigational
PantoprazoleThe metabolism of Pantoprazole can be decreased when combined with Midostaurin.Approved
ParamethadioneThe metabolism of Paramethadione can be decreased when combined with Midostaurin.Approved
ParecoxibThe serum concentration of Parecoxib can be increased when it is combined with Midostaurin.Approved
ParoxetineThe metabolism of Paroxetine can be decreased when combined with Midostaurin.Approved, Investigational
PazopanibThe metabolism of Pazopanib can be decreased when combined with Midostaurin.Approved
PentamidineThe metabolism of Pentamidine can be decreased when combined with Midostaurin.Approved
PentobarbitalThe metabolism of Midostaurin can be increased when combined with Pentobarbital.Approved, Vet Approved
PentoxifyllineThe serum concentration of Pentoxifylline can be increased when it is combined with Midostaurin.Approved, Investigational
PerhexilineThe metabolism of Perhexiline can be decreased when combined with Midostaurin.Approved, Investigational
PerospironeThe metabolism of Perospirone can be decreased when combined with Midostaurin.Approved
PerphenazineThe metabolism of Perphenazine can be decreased when combined with Midostaurin.Approved
PeruvosidePeruvoside may decrease the cardiotoxic activities of Midostaurin.Experimental
PethidineThe metabolism of Pethidine can be decreased when combined with Midostaurin.Approved
PhenacetinThe metabolism of Phenacetin can be decreased when combined with Midostaurin.Withdrawn
PhenforminThe metabolism of Phenformin can be decreased when combined with Midostaurin.Approved, Investigational, Withdrawn
PhenobarbitalThe metabolism of Midostaurin can be increased when combined with Phenobarbital.Approved
PhenprocoumonThe metabolism of Phenprocoumon can be decreased when combined with Midostaurin.Approved, Investigational
PhenylbutazoneThe metabolism of Phenylbutazone can be decreased when combined with Midostaurin.Approved, Vet Approved
PhenytoinThe metabolism of Midostaurin can be increased when combined with Phenytoin.Approved, Vet Approved
PimozideThe serum concentration of Pimozide can be increased when it is combined with Midostaurin.Approved
PindololThe metabolism of Pindolol can be decreased when combined with Midostaurin.Approved
PioglitazoneThe metabolism of Pioglitazone can be decreased when combined with Midostaurin.Approved, Investigational
PiperazineThe metabolism of Piperazine can be decreased when combined with Midostaurin.Approved, Vet Approved
PipotiazineThe metabolism of Pipotiazine can be decreased when combined with Midostaurin.Approved, Investigational
PirfenidoneThe serum concentration of Pirfenidone can be increased when it is combined with Midostaurin.Approved, Investigational
PiroxicamThe metabolism of Piroxicam can be decreased when combined with Midostaurin.Approved, Investigational
PitavastatinThe metabolism of Pitavastatin can be decreased when combined with Midostaurin.Approved
PomalidomideThe serum concentration of Pomalidomide can be increased when it is combined with Midostaurin.Approved
PonatinibThe metabolism of Ponatinib can be decreased when combined with Midostaurin.Approved
PosaconazoleThe metabolism of Midostaurin can be decreased when combined with Posaconazole.Approved, Investigational, Vet Approved
PrasugrelThe metabolism of Prasugrel can be decreased when combined with Midostaurin.Approved
PravastatinThe metabolism of Pravastatin can be decreased when combined with Midostaurin.Approved
PraziquantelThe metabolism of Praziquantel can be decreased when combined with Midostaurin.Approved, Vet Approved
PrimaquineThe metabolism of Primaquine can be decreased when combined with Midostaurin.Approved
PrimidoneThe metabolism of Midostaurin can be increased when combined with Primidone.Approved, Vet Approved
ProcainamideThe metabolism of Procainamide can be decreased when combined with Midostaurin.Approved
ProchlorperazineThe metabolism of Prochlorperazine can be decreased when combined with Midostaurin.Approved, Vet Approved
ProgesteroneThe metabolism of Progesterone can be decreased when combined with Midostaurin.Approved, Vet Approved
ProguanilThe metabolism of Proguanil can be decreased when combined with Midostaurin.Approved
PromazineThe metabolism of Promazine can be decreased when combined with Midostaurin.Approved, Vet Approved
PromethazineThe metabolism of Promethazine can be decreased when combined with Midostaurin.Approved
PropafenoneThe serum concentration of Propafenone can be increased when it is combined with Midostaurin.Approved
PropofolThe metabolism of Propofol can be decreased when combined with Midostaurin.Approved, Investigational, Vet Approved
PropranololThe metabolism of Propranolol can be decreased when combined with Midostaurin.Approved, Investigational
ProscillaridinProscillaridin may decrease the cardiotoxic activities of Midostaurin.Experimental
ProtriptylineThe metabolism of Protriptyline can be decreased when combined with Midostaurin.Approved
PseudoephedrineThe metabolism of Pseudoephedrine can be decreased when combined with Midostaurin.Approved
PyrazinamideThe metabolism of Pyrazinamide can be decreased when combined with Midostaurin.Approved
QuazepamThe metabolism of Quazepam can be decreased when combined with Midostaurin.Approved, Illicit
QuetiapineThe metabolism of Quetiapine can be decreased when combined with Midostaurin.Approved
QuinidineThe metabolism of Quinidine can be decreased when combined with Midostaurin.Approved
QuinineThe metabolism of Quinine can be decreased when combined with Midostaurin.Approved
RamelteonThe serum concentration of Ramelteon can be increased when it is combined with Midostaurin.Approved, Investigational
RanitidineThe metabolism of Ranitidine can be decreased when combined with Midostaurin.Approved
RanolazineThe metabolism of Midostaurin can be decreased when combined with Ranolazine.Approved, Investigational
RasagilineThe serum concentration of Rasagiline can be increased when it is combined with Midostaurin.Approved
RemoxiprideThe metabolism of Remoxipride can be decreased when combined with Midostaurin.Approved, Withdrawn
repinotanThe metabolism of repinotan can be decreased when combined with Midostaurin.Investigational
ResveratrolThe metabolism of Resveratrol can be decreased when combined with Midostaurin.Approved, Experimental, Investigational
RibociclibThe serum concentration of Ribociclib can be increased when it is combined with Midostaurin.Approved
RifabutinThe metabolism of Midostaurin can be increased when combined with Rifabutin.Approved
RifampicinThe metabolism of Midostaurin can be increased when combined with Rifampicin.Approved
RifapentineThe metabolism of Midostaurin can be increased when combined with Rifapentine.Approved
RiluzoleThe metabolism of Riluzole can be decreased when combined with Midostaurin.Approved, Investigational
RisperidoneThe metabolism of Risperidone can be decreased when combined with Midostaurin.Approved, Investigational
RitonavirThe metabolism of Ritonavir can be decreased when combined with Midostaurin.Approved, Investigational
RizatriptanThe metabolism of Rizatriptan can be decreased when combined with Midostaurin.Approved
RofecoxibThe metabolism of Rofecoxib can be decreased when combined with Midostaurin.Investigational, Withdrawn
RopiniroleThe metabolism of Ropinirole can be decreased when combined with Midostaurin.Approved, Investigational
RopivacaineThe metabolism of Ropivacaine can be decreased when combined with Midostaurin.Approved
RosiglitazoneThe metabolism of Rosiglitazone can be decreased when combined with Midostaurin.Approved, Investigational
RosuvastatinThe metabolism of Rosuvastatin can be decreased when combined with Midostaurin.Approved
RotigotineThe metabolism of Rotigotine can be decreased when combined with Midostaurin.Approved
RucaparibThe metabolism of Rucaparib can be decreased when combined with Midostaurin.Approved, Investigational
RupatadineThe metabolism of Rupatadine can be decreased when combined with Midostaurin.Approved
Salicylic acidThe metabolism of Salicylic acid can be decreased when combined with Midostaurin.Approved, Vet Approved
SaquinavirThe metabolism of Midostaurin can be decreased when combined with Saquinavir.Approved, Investigational
SaxagliptinThe serum concentration of Saxagliptin can be decreased when it is combined with Midostaurin.Approved
SelegilineThe metabolism of Selegiline can be decreased when combined with Midostaurin.Approved, Investigational, Vet Approved
SeratrodastThe metabolism of Seratrodast can be decreased when combined with Midostaurin.Approved
SertindoleThe metabolism of Sertindole can be decreased when combined with Midostaurin.Approved, Investigational, Withdrawn
SertralineThe metabolism of Sertraline can be decreased when combined with Midostaurin.Approved
SildenafilThe metabolism of Sildenafil can be decreased when combined with Midostaurin.Approved, Investigational
SiltuximabThe serum concentration of Midostaurin can be decreased when it is combined with Siltuximab.Approved
SimeprevirThe serum concentration of Midostaurin can be increased when it is combined with Simeprevir.Approved
SimvastatinThe metabolism of Simvastatin can be decreased when combined with Midostaurin.Approved
SitaxentanThe metabolism of Sitaxentan can be decreased when combined with Midostaurin.Approved, Investigational, Withdrawn
SparteineThe metabolism of Sparteine can be decreased when combined with Midostaurin.Experimental
St. John's WortThe serum concentration of Midostaurin can be decreased when it is combined with St. John's Wort.Investigational, Nutraceutical
StiripentolThe serum concentration of Midostaurin can be increased when it is combined with Stiripentol.Approved
SulfadiazineThe metabolism of Sulfadiazine can be decreased when combined with Midostaurin.Approved, Vet Approved
SulfamethoxazoleThe metabolism of Sulfamethoxazole can be decreased when combined with Midostaurin.Approved
SulfamoxoleThe metabolism of Sulfamoxole can be decreased when combined with Midostaurin.Approved
SulfinpyrazoneThe metabolism of Sulfinpyrazone can be decreased when combined with Midostaurin.Approved
SulfisoxazoleThe metabolism of Sulfisoxazole can be decreased when combined with Midostaurin.Approved, Vet Approved
SuprofenThe metabolism of Suprofen can be decreased when combined with Midostaurin.Approved, Withdrawn
TacrineThe metabolism of Tacrine can be decreased when combined with Midostaurin.Investigational, Withdrawn
TamoxifenThe serum concentration of the active metabolites of Tamoxifen can be reduced when Tamoxifen is used in combination with Midostaurin resulting in a loss in efficacy.Approved
TamsulosinThe serum concentration of Tamsulosin can be increased when it is combined with Midostaurin.Approved, Investigational
TapentadolThe metabolism of Tapentadol can be decreased when combined with Midostaurin.Approved
TasimelteonThe serum concentration of Tasimelteon can be increased when it is combined with Midostaurin.Approved
TegaserodThe metabolism of Tegaserod can be decreased when combined with Midostaurin.Investigational, Withdrawn
TelaprevirThe metabolism of Midostaurin can be decreased when combined with Telaprevir.Approved, Withdrawn
TelithromycinThe metabolism of Midostaurin can be decreased when combined with Telithromycin.Approved
TemafloxacinThe metabolism of Temafloxacin can be decreased when combined with Midostaurin.Withdrawn
TemazepamThe metabolism of Temazepam can be decreased when combined with Midostaurin.Approved
TenoxicamThe metabolism of Tenoxicam can be decreased when combined with Midostaurin.Approved
TerbinafineThe metabolism of Terbinafine can be decreased when combined with Midostaurin.Approved, Investigational, Vet Approved
TerfenadineThe metabolism of Terfenadine can be decreased when combined with Midostaurin.Withdrawn
TesmilifeneThe metabolism of Tesmilifene can be decreased when combined with Midostaurin.Investigational
TestosteroneThe metabolism of Testosterone can be decreased when combined with Midostaurin.Approved, Investigational
TetrabenazineThe serum concentration of Tetrabenazine can be increased when it is combined with Midostaurin.Approved
ThalidomideThe metabolism of Thalidomide can be decreased when combined with Midostaurin.Approved, Investigational, Withdrawn
TheobromineThe metabolism of Theobromine can be decreased when combined with Midostaurin.Approved, Investigational
TheophyllineThe metabolism of Theophylline can be decreased when combined with Midostaurin.Approved
ThiabendazoleThe metabolism of Thiabendazole can be decreased when combined with Midostaurin.Approved, Vet Approved
ThiamylalThe metabolism of Thiamylal can be decreased when combined with Midostaurin.Approved, Vet Approved
ThioridazineThe serum concentration of Thioridazine can be increased when it is combined with Midostaurin.Approved, Withdrawn
ThiothixeneThe metabolism of Thiothixene can be decreased when combined with Midostaurin.Approved
TiclopidineThe metabolism of Ticlopidine can be decreased when combined with Midostaurin.Approved
TimololThe metabolism of Timolol can be decreased when combined with Midostaurin.Approved
TiotropiumThe metabolism of Tiotropium can be decreased when combined with Midostaurin.Approved
TipranavirThe metabolism of Tipranavir can be decreased when combined with Midostaurin.Approved, Investigational
TizanidineThe serum concentration of Tizanidine can be increased when it is combined with Midostaurin.Approved
TocilizumabThe serum concentration of Midostaurin can be decreased when it is combined with Tocilizumab.Approved
TolbutamideThe metabolism of Tolbutamide can be decreased when combined with Midostaurin.Approved
TolterodineThe metabolism of Tolterodine can be decreased when combined with Midostaurin.Approved, Investigational
TorasemideThe metabolism of Torasemide can be decreased when combined with Midostaurin.Approved
ToremifeneThe metabolism of Toremifene can be decreased when combined with Midostaurin.Approved, Investigational
TrabectedinThe metabolism of Trabectedin can be decreased when combined with Midostaurin.Approved, Investigational
TramadolThe therapeutic efficacy of Tramadol can be decreased when used in combination with Midostaurin.Approved, Investigational
TrastuzumabTrastuzumab may increase the cardiotoxic activities of Midostaurin.Approved, Investigational
TrazodoneThe metabolism of Trazodone can be decreased when combined with Midostaurin.Approved, Investigational
TreprostinilThe metabolism of Treprostinil can be decreased when combined with Midostaurin.Approved, Investigational
TretinoinThe metabolism of Tretinoin can be decreased when combined with Midostaurin.Approved, Investigational, Nutraceutical
TriamtereneThe metabolism of Triamterene can be decreased when combined with Midostaurin.Approved
TrifluoperazineThe metabolism of Trifluoperazine can be decreased when combined with Midostaurin.Approved
TrimethadioneThe metabolism of Trimethadione can be decreased when combined with Midostaurin.Approved
TrimethoprimThe metabolism of Trimethoprim can be decreased when combined with Midostaurin.Approved, Vet Approved
TrimipramineThe metabolism of Trimipramine can be decreased when combined with Midostaurin.Approved
TroglitazoneThe metabolism of Troglitazone can be decreased when combined with Midostaurin.Investigational, Withdrawn
UlipristalThe metabolism of Ulipristal can be decreased when combined with Midostaurin.Approved
UmeclidiniumThe metabolism of Umeclidinium can be decreased when combined with Midostaurin.Approved
VadimezanThe metabolism of Vadimezan can be decreased when combined with Midostaurin.Investigational
ValbenazineThe metabolism of Valbenazine can be decreased when combined with Midostaurin.Approved, Investigational
ValdecoxibThe metabolism of Valdecoxib can be decreased when combined with Midostaurin.Investigational, Withdrawn
Valproic AcidThe metabolism of Valproic Acid can be decreased when combined with Midostaurin.Approved, Investigational
ValsartanThe metabolism of Valsartan can be decreased when combined with Midostaurin.Approved, Investigational
VenlafaxineThe metabolism of Venlafaxine can be decreased when combined with Midostaurin.Approved
VerapamilThe metabolism of Verapamil can be decreased when combined with Midostaurin.Approved
VernakalantThe metabolism of Vernakalant can be decreased when combined with Midostaurin.Approved, Investigational
VicrivirocThe metabolism of Vicriviroc can be decreased when combined with Midostaurin.Investigational
VilazodoneThe metabolism of Vilazodone can be decreased when combined with Midostaurin.Approved
VinblastineThe metabolism of Vinblastine can be decreased when combined with Midostaurin.Approved
VinorelbineThe metabolism of Vinorelbine can be decreased when combined with Midostaurin.Approved, Investigational
VismodegibThe metabolism of Vismodegib can be decreased when combined with Midostaurin.Approved
VoriconazoleThe metabolism of Midostaurin can be decreased when combined with Voriconazole.Approved, Investigational
VortioxetineThe serum concentration of Vortioxetine can be increased when it is combined with Midostaurin.Approved
VoxilaprevirThe metabolism of Voxilaprevir can be decreased when combined with Midostaurin.Approved
WarfarinThe metabolism of Warfarin can be decreased when combined with Midostaurin.Approved
XimelagatranThe metabolism of Ximelagatran can be decreased when combined with Midostaurin.Approved, Investigational, Withdrawn
YohimbineThe metabolism of Yohimbine can be decreased when combined with Midostaurin.Approved, Vet Approved
ZafirlukastThe metabolism of Zafirlukast can be decreased when combined with Midostaurin.Approved, Investigational
ZalcitabineThe metabolism of Zalcitabine can be decreased when combined with Midostaurin.Approved, Investigational
ZaltoprofenThe metabolism of Zaltoprofen can be decreased when combined with Midostaurin.Approved, Investigational
ZidovudineThe metabolism of Zidovudine can be decreased when combined with Midostaurin.Approved
ZileutonThe metabolism of Zileuton can be decreased when combined with Midostaurin.Approved, Investigational, Withdrawn
ZiprasidoneThe metabolism of Ziprasidone can be decreased when combined with Midostaurin.Approved
ZolmitriptanThe metabolism of Zolmitriptan can be decreased when combined with Midostaurin.Approved, Investigational
ZolpidemThe metabolism of Zolpidem can be decreased when combined with Midostaurin.Approved
ZopicloneThe metabolism of Zopiclone can be decreased when combined with Midostaurin.Approved
ZuclopenthixolThe metabolism of Zuclopenthixol can be decreased when combined with Midostaurin.Approved, Investigational
Food Interactions
Not Available

References

General References
  1. Fischer T, Stone RM, Deangelo DJ, Galinsky I, Estey E, Lanza C, Fox E, Ehninger G, Feldman EJ, Schiller GJ, Klimek VM, Nimer SD, Gilliland DG, Dutreix C, Huntsman-Labed A, Virkus J, Giles FJ: Phase IIB trial of oral Midostaurin (PKC412), the FMS-like tyrosine kinase 3 receptor (FLT3) and multi-targeted kinase inhibitor, in patients with acute myeloid leukemia and high-risk myelodysplastic syndrome with either wild-type or mutated FLT3. J Clin Oncol. 2010 Oct 1;28(28):4339-45. doi: 10.1200/JCO.2010.28.9678. Epub 2010 Aug 23. [PubMed:20733134]
  2. Millward MJ, House C, Bowtell D, Webster L, Olver IN, Gore M, Copeman M, Lynch K, Yap A, Wang Y, Cohen PS, Zalcberg J: The multikinase inhibitor midostaurin (PKC412A) lacks activity in metastatic melanoma: a phase IIA clinical and biologic study. Br J Cancer. 2006 Oct 9;95(7):829-34. Epub 2006 Sep 12. [PubMed:16969355]
  3. Gotlib J, Kluin-Nelemans HC, George TI, Akin C, Sotlar K, Hermine O, Awan FT, Hexner E, Mauro MJ, Sternberg DW, Villeneuve M, Huntsman Labed A, Stanek EJ, Hartmann K, Horny HP, Valent P, Reiter A: Efficacy and Safety of Midostaurin in Advanced Systemic Mastocytosis. N Engl J Med. 2016 Jun 30;374(26):2530-41. doi: 10.1056/NEJMoa1513098. [PubMed:27355533]
  4. Gallogly MM, Lazarus HM: Midostaurin: an emerging treatment for acute myeloid leukemia patients. J Blood Med. 2016 Apr 19;7:73-83. doi: 10.2147/JBM.S100283. eCollection 2016. [PubMed:27186148]
  5. Yin OQ, Wang Y, Schran H: A mechanism-based population pharmacokinetic model for characterizing time-dependent pharmacokinetics of midostaurin and its metabolites in human subjects. Clin Pharmacokinet. 2008;47(12):807-16. doi: 10.2165/0003088-200847120-00005. [PubMed:19026036]
  6. Abmole Midostaurin MSDS [Link]
  7. Alfa Aesar Midostaurin MSDS [Link]
  8. Cayman Midostaurin MSDS [Link]
External Links
KEGG Drug
D05029
PubChem Compound
9829523
PubChem Substance
347827778
ChemSpider
8005258
BindingDB
50326053
ChEBI
63452
ChEMBL
CHEMBL608533
HET
2K2
Drugs.com
Drugs.com Drug Page
AHFS Codes
  • 10:00.00 — Antineoplastic Agents
PDB Entries
4nct
FDA label
Download (306 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1Active Not RecruitingTreatmentAdenocarcinoma of the Rectum1
1Active Not RecruitingTreatmentLeukemia Acute Myeloid Leukemia (AML) / Myelodysplastic Syndrome1
1CompletedTreatmentAcute Myeloid Leukemia With Multilineage Dysplasia Following / Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities / Adult Acute Myeloid Leukemia With Del(5q) / Adult Acute Myeloid Leukemia With Inv(16)(p13;q22) / Adult Acute Myeloid Leukemia With T(15;17)(q22;q12) / Adult Acute Myeloid Leukemia With T(16;16)(p13;q22) / Adult Acute Myeloid Leukemia With T(8;21)(q22;q22) / Leukemia Acute Myeloid Leukemia (AML) / Myelodysplastic Syndrome / Recurrent Adult Acute Myeloid Leukemia / Secondary Acute Myeloid Leukemia1
1CompletedTreatmentLeukemia Acute Myeloid Leukemia (AML)3
1RecruitingBasic ScienceHepatic Impairment1
1RecruitingTreatmentAML and High Risk MDS1
1, 2Active Not RecruitingTreatmentUntreated Adult Acute Myeloid Leukemia1
1, 2CompletedTreatmentLeukemia Acute Myeloid Leukemia (AML) / Myelodysplastic Syndrome1
1, 2CompletedTreatmentLeukemia Acute Myeloid Leukemia (AML) / Myelodysplastic Syndromes1
1, 2CompletedTreatmentLeukemias1
1, 2TerminatedTreatmentAcute Lymphoblastic Leukaemias (ALL) / Leukemia Acute Myeloid Leukemia (AML)1
2Active Not RecruitingTreatmentAcute Myeloid Leukemia (AML) With Multilineage Dysplasia Following Myelodysplastic Syndrome, in Adults / Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome / Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities / Adult Acute Myeloid Leukemia With Del(5q) / Adult Acute Myeloid Leukemia With Inv(16)(p13;q22) / Adult Acute Myeloid Leukemia With T(16;16)(p13;q22) / Adult Acute Myeloid Leukemia With T(8;21)(q22;q22) / AML (Adult) With 11q23 (MLL) Abnormalities / AML (Adult) With Del(5q) / AML (Adult) With Inv(16)(p13;q22) / AML (Adult) With t(16;16)(p13;q22) / AML (Adult) With t(8;21)(q22;q22) / Secondary Acute Myeloid Leukemia / Secondary AML (Adult) / Untreated Adult Acute Myeloid Leukemia / Untreated AML (Adult)1
2Active Not RecruitingTreatmentHematological Non-mast Cell Lineage Disease (AHNMD) / Malignant mast cell neoplasm / Systemic Mastocytosis, Aggressive (ASM)1
2Active Not RecruitingTreatmentLeukemias1
2Not Yet RecruitingTreatmentAcute Myeloid Leukemia With Gene Mutations / Adult Acute Myeloid Leukemia in Remission1
2Not Yet RecruitingTreatmentLeukemia Acute Myeloid Leukemia (AML)2
2RecruitingPreventionLeukemia Acute Myeloid Leukemia (AML)1
2RecruitingTreatmentAcute Myeloid Leukemia With FLT3/ITD Mutation / Acute Myeloid Leukemia With Gene Mutations / FLT3 Tyrosine Kinase Domain Point Mutation / Secondary Acute Myeloid Leukemia / Untreated Adult Acute Myeloid Leukemia1
2RecruitingTreatmentLeukemia Acute Myeloid Leukemia (AML)3
2Unknown StatusTreatmentIndolent Systemic Mastocytosis1
2, 3Not Yet RecruitingTreatmentAdult Myelodysplastic Syndrome / Leukemia Acute Myeloid Leukemia (AML) / Myelodysplastic Syndrome With Excess Blasts-2 / Untreated Adult Acute Myeloid Leukemia1
3Active Not RecruitingTreatmentLeukemias1
3Not Yet RecruitingTreatmentNewly Diagnosed FLT3 Mutated AML1
Not AvailableAvailableNot AvailableAcute Myeloid Leukemia (AML) With / FLT3 Mutation, Internal Tandem Duplication (ITD) or Tyrosine Kinase Domain (TKD)1
Not AvailableAvailableNot AvailableFLT3-Mutated Acute Myeloid Leukemia1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
CapsuleOral25 mg
Capsule, liquid filledOral25 mg/1
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US8575146No2010-12-022030-12-02Us
US7973031No2004-10-172024-10-17Us
US8222244No2002-10-292022-10-29Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)235-260Alfa Aesar MSDS
water solubility<1mg/mLAbmole MSDS
logP5.89Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0157 mg/mLALOGPS
logP4.52ALOGPS
logP5.43ChemAxon
logS-4.6ALOGPS
pKa (Strongest Acidic)13.45ChemAxon
pKa (Strongest Basic)-0.83ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area77.73 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity162.61 m3·mol-1ChemAxon
Polarizability60.58 Å3ChemAxon
Number of Rings9ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as indolocarbazoles. These are polycyclic aromatic compounds containing an indole fused to a carbazole.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Indoles and derivatives
Sub Class
Carbazoles
Direct Parent
Indolocarbazoles
Alternative Parents
Pyrrolo[2,3-a]carbazoles / Pyrroloindoles / Isoindolones / Benzamides / Indoles / Benzoyl derivatives / Oxanes / Tertiary carboxylic acid amides / Heteroaromatic compounds / Pyrroles
show 9 more
Substituents
Indolocarbazole / Pyrrolo[2,3-a]carbazole / Pyrroloindole / Isoindolone / Benzamide / Benzoic acid or derivatives / Isoindole or derivatives / Isoindoline / Indole / Benzoyl
show 22 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
benzamides, gamma-lactam, organic heterooctacyclic compound, indolocarbazole (CHEBI:63452)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
Inhibitor
General Function
Zinc ion binding
Specific Function
Calcium-activated, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that is involved in positive and negative regulation of cell proliferation, apoptosis, differenti...
Gene Name
PRKCA
Uniprot ID
P17252
Uniprot Name
Protein kinase C alpha type
Molecular Weight
76749.445 Da
References
  1. Millward MJ, House C, Bowtell D, Webster L, Olver IN, Gore M, Copeman M, Lynch K, Yap A, Wang Y, Cohen PS, Zalcberg J: The multikinase inhibitor midostaurin (PKC412A) lacks activity in metastatic melanoma: a phase IIA clinical and biologic study. Br J Cancer. 2006 Oct 9;95(7):829-34. Epub 2006 Sep 12. [PubMed:16969355]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
Inhibitor
General Function
Vascular endothelial growth factor-activated receptor activity
Specific Function
Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD. Plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and ...
Gene Name
KDR
Uniprot ID
P35968
Uniprot Name
Vascular endothelial growth factor receptor 2
Molecular Weight
151525.555 Da
References
  1. Millward MJ, House C, Bowtell D, Webster L, Olver IN, Gore M, Copeman M, Lynch K, Yap A, Wang Y, Cohen PS, Zalcberg J: The multikinase inhibitor midostaurin (PKC412A) lacks activity in metastatic melanoma: a phase IIA clinical and biologic study. Br J Cancer. 2006 Oct 9;95(7):829-34. Epub 2006 Sep 12. [PubMed:16969355]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
Inhibitor
General Function
Transmembrane receptor protein tyrosine kinase activity
Specific Function
Tyrosine-protein kinase that acts as cell-surface receptor for the cytokine KITLG/SCF and plays an essential role in the regulation of cell survival and proliferation, hematopoiesis, stem cell main...
Gene Name
KIT
Uniprot ID
P10721
Uniprot Name
Mast/stem cell growth factor receptor Kit
Molecular Weight
109863.655 Da
References
  1. Millward MJ, House C, Bowtell D, Webster L, Olver IN, Gore M, Copeman M, Lynch K, Yap A, Wang Y, Cohen PS, Zalcberg J: The multikinase inhibitor midostaurin (PKC412A) lacks activity in metastatic melanoma: a phase IIA clinical and biologic study. Br J Cancer. 2006 Oct 9;95(7):829-34. Epub 2006 Sep 12. [PubMed:16969355]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
Inhibitor
General Function
Vascular endothelial growth factor-activated receptor activity
Specific Function
Tyrosine-protein kinase that acts as a cell-surface receptor for PDGFA, PDGFB and PDGFC and plays an essential role in the regulation of embryonic development, cell proliferation, survival and chem...
Gene Name
PDGFRA
Uniprot ID
P16234
Uniprot Name
Platelet-derived growth factor receptor alpha
Molecular Weight
122668.46 Da
References
  1. Millward MJ, House C, Bowtell D, Webster L, Olver IN, Gore M, Copeman M, Lynch K, Yap A, Wang Y, Cohen PS, Zalcberg J: The multikinase inhibitor midostaurin (PKC412A) lacks activity in metastatic melanoma: a phase IIA clinical and biologic study. Br J Cancer. 2006 Oct 9;95(7):829-34. Epub 2006 Sep 12. [PubMed:16969355]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
Inhibitor
General Function
Vascular endothelial growth factor binding
Specific Function
Tyrosine-protein kinase that acts as cell-surface receptor for homodimeric PDGFB and PDGFD and for heterodimers formed by PDGFA and PDGFB, and plays an essential role in the regulation of embryonic...
Gene Name
PDGFRB
Uniprot ID
P09619
Uniprot Name
Platelet-derived growth factor receptor beta
Molecular Weight
123966.895 Da
References
  1. Millward MJ, House C, Bowtell D, Webster L, Olver IN, Gore M, Copeman M, Lynch K, Yap A, Wang Y, Cohen PS, Zalcberg J: The multikinase inhibitor midostaurin (PKC412A) lacks activity in metastatic melanoma: a phase IIA clinical and biologic study. Br J Cancer. 2006 Oct 9;95(7):829-34. Epub 2006 Sep 12. [PubMed:16969355]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
Inhibitor
General Function
Vascular endothelial growth factor-activated receptor activity
Specific Function
Tyrosine-protein kinase that acts as cell-surface receptor for the cytokine FLT3LG and regulates differentiation, proliferation and survival of hematopoietic progenitor cells and of dendritic cells...
Gene Name
FLT3
Uniprot ID
P36888
Uniprot Name
Receptor-type tyrosine-protein kinase FLT3
Molecular Weight
112902.51 Da
References
  1. Millward MJ, House C, Bowtell D, Webster L, Olver IN, Gore M, Copeman M, Lynch K, Yap A, Wang Y, Cohen PS, Zalcberg J: The multikinase inhibitor midostaurin (PKC412A) lacks activity in metastatic melanoma: a phase IIA clinical and biologic study. Br J Cancer. 2006 Oct 9;95(7):829-34. Epub 2006 Sep 12. [PubMed:16969355]
  2. Gallogly MM, Lazarus HM: Midostaurin: an emerging treatment for acute myeloid leukemia patients. J Blood Med. 2016 Apr 19;7:73-83. doi: 10.2147/JBM.S100283. eCollection 2016. [PubMed:27186148]

Enzymes

1. Cytochrome p450 3A subfamily
Kind
Protein group
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
Inducer
References
  1. He H, Tran P, Gu H, Tedesco V, Zhang J, Lin W, Gatlik E, Klein K, Heimbach T: Midostaurin, a Novel Protein Kinase Inhibitor for the Treatment of Acute Myelogenous Leukemia: Insights from Human Absorption, Metabolism, and Excretion Studies of a BDDCS II Drug. Drug Metab Dispos. 2017 May;45(5):540-555. doi: 10.1124/dmd.116.072744. Epub 2017 Mar 7. [PubMed:28270565]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
Inducer
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
References
  1. He H, Tran P, Gu H, Tedesco V, Zhang J, Lin W, Gatlik E, Klein K, Heimbach T: Midostaurin, a Novel Protein Kinase Inhibitor for the Treatment of Acute Myelogenous Leukemia: Insights from Human Absorption, Metabolism, and Excretion Studies of a BDDCS II Drug. Drug Metab Dispos. 2017 May;45(5):540-555. doi: 10.1124/dmd.116.072744. Epub 2017 Mar 7. [PubMed:28270565]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inducer
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2B6
Uniprot ID
P20813
Uniprot Name
Cytochrome P450 2B6
Molecular Weight
56277.81 Da
References
  1. He H, Tran P, Gu H, Tedesco V, Zhang J, Lin W, Gatlik E, Klein K, Heimbach T: Midostaurin, a Novel Protein Kinase Inhibitor for the Treatment of Acute Myelogenous Leukemia: Insights from Human Absorption, Metabolism, and Excretion Studies of a BDDCS II Drug. Drug Metab Dispos. 2017 May;45(5):540-555. doi: 10.1124/dmd.116.072744. Epub 2017 Mar 7. [PubMed:28270565]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
Inducer
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
References
  1. He H, Tran P, Gu H, Tedesco V, Zhang J, Lin W, Gatlik E, Klein K, Heimbach T: Midostaurin, a Novel Protein Kinase Inhibitor for the Treatment of Acute Myelogenous Leukemia: Insights from Human Absorption, Metabolism, and Excretion Studies of a BDDCS II Drug. Drug Metab Dispos. 2017 May;45(5):540-555. doi: 10.1124/dmd.116.072744. Epub 2017 Mar 7. [PubMed:28270565]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
Inducer
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. He H, Tran P, Gu H, Tedesco V, Zhang J, Lin W, Gatlik E, Klein K, Heimbach T: Midostaurin, a Novel Protein Kinase Inhibitor for the Treatment of Acute Myelogenous Leukemia: Insights from Human Absorption, Metabolism, and Excretion Studies of a BDDCS II Drug. Drug Metab Dispos. 2017 May;45(5):540-555. doi: 10.1124/dmd.116.072744. Epub 2017 Mar 7. [PubMed:28270565]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
Inducer
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
References
  1. He H, Tran P, Gu H, Tedesco V, Zhang J, Lin W, Gatlik E, Klein K, Heimbach T: Midostaurin, a Novel Protein Kinase Inhibitor for the Treatment of Acute Myelogenous Leukemia: Insights from Human Absorption, Metabolism, and Excretion Studies of a BDDCS II Drug. Drug Metab Dispos. 2017 May;45(5):540-555. doi: 10.1124/dmd.116.072744. Epub 2017 Mar 7. [PubMed:28270565]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. He H, Tran P, Gu H, Tedesco V, Zhang J, Lin W, Gatlik E, Klein K, Heimbach T: Midostaurin, a Novel Protein Kinase Inhibitor for the Treatment of Acute Myelogenous Leukemia: Insights from Human Absorption, Metabolism, and Excretion Studies of a BDDCS II Drug. Drug Metab Dispos. 2017 May;45(5):540-555. doi: 10.1124/dmd.116.072744. Epub 2017 Mar 7. [PubMed:28270565]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic ...
Gene Name
CYP2E1
Uniprot ID
P05181
Uniprot Name
Cytochrome P450 2E1
Molecular Weight
56848.42 Da
References
  1. He H, Tran P, Gu H, Tedesco V, Zhang J, Lin W, Gatlik E, Klein K, Heimbach T: Midostaurin, a Novel Protein Kinase Inhibitor for the Treatment of Acute Myelogenous Leukemia: Insights from Human Absorption, Metabolism, and Excretion Studies of a BDDCS II Drug. Drug Metab Dispos. 2017 May;45(5):540-555. doi: 10.1124/dmd.116.072744. Epub 2017 Mar 7. [PubMed:28270565]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inducer
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inducer
General Function
Oxygen binding
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inducer
General Function
Oxygen binding
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP3A7
Uniprot ID
P24462
Uniprot Name
Cytochrome P450 3A7
Molecular Weight
57525.03 Da
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inducer
General Function
Monooxygenase activity
Specific Function
Exhibits low testosterone 6-beta-hydroxylase activity.
Gene Name
CYP3A43
Uniprot ID
Q9HB55
Uniprot Name
Cytochrome P450 3A43
Molecular Weight
57669.21 Da

Drug created on March 19, 2008 10:39 / Updated on November 19, 2017 20:33