Identification

Name
Regorafenib
Accession Number
DB08896
Type
Small Molecule
Groups
Approved
Description

Regorafenib is an orally-administered inhibitor of multiple kinases. It is used for the treatment of metastatic colorectal cancer and advanced gastrointestinal stromal tumours. FDA approved on September 27, 2012. Approved use of Regorafenib was expanded to treat Hepatocellular Carcinoma in April, 2017.

Structure
Thumb
Synonyms
  • Regorafenib
  • Régorafénib
  • Regorafenibum
External IDs
BAY 73-4506 / BAY-73-4506 / BAY-734506
Product Ingredients
IngredientUNIICASInChI Key
Regorafenib monohydrateMGN125FS9D1019206-88-2ZOPOQLDXFHBOIH-UHFFFAOYSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
StivargaTablet40 mgOralBayer2013-04-02Not applicableCanada
StivargaTablet, film coated40 mg/1OralBayer2012-09-27Not applicableUs
StivargaTablet, film coated40 mgOralBayer Pharma Ag2013-08-26Not applicableEu
StivargaTablet, film coated40 mgOralBayer Pharma Ag2013-08-26Not applicableEu
Categories
UNII
24T2A1DOYB
CAS number
755037-03-7
Weight
Average: 482.815
Monoisotopic: 482.076880893
Chemical Formula
C21H15ClF4N4O3
InChI Key
FNHKPVJBJVTLMP-UHFFFAOYSA-N
InChI
InChI=1S/C21H15ClF4N4O3/c1-27-19(31)18-10-13(6-7-28-18)33-12-3-5-17(16(23)9-12)30-20(32)29-11-2-4-15(22)14(8-11)21(24,25)26/h2-10H,1H3,(H,27,31)(H2,29,30,32)
IUPAC Name
4-[4-({[4-chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)-3-fluorophenoxy]-N-methylpyridine-2-carboxamide
SMILES
CNC(=O)C1=CC(OC2=CC(F)=C(NC(=O)NC3=CC=C(Cl)C(=C3)C(F)(F)F)C=C2)=CC=N1

Pharmacology

Indication

Regorafenib is indicated for the treatment of patients with metastatic colorectal cancer (CRC) who have been previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF therapy, and, if KRAS wild type, an anti-EGFR therapy. Regorafenib is also indicated for the treatment of patients with locally advanced, unresectable or metastatic gastrointestinal stromal tumor (GIST) who have been previously treated with imatinib mesylate and sunitinib malate.

Structured Indications
Pharmacodynamics
Not Available
Mechanism of action

Regorafenib is a small molecule inhibitor of multiple membrane-bound and intracellular kinases involved in normal cellular functions and in pathologic processes such as oncogenesis, tumor angiogenesis, and maintenance of the tumor microenvironment. In in vitro biochemical or cellular assays, regorafenib or its major human active metabolites M-2 and M-5 inhibited the activity of RET, VEGFR1, VEGFR2, VEGFR3, KIT, PDGFR-alpha, PDGFR-beta, FGFR1, FGFR2, TIE2, DDR2, TrkA, Eph2A, RAF-1, BRAF, BRAFV600E , SAPK2, PTK5, and Abl at concentrations of regorafenib that have been achieved clinically. In in vivo models, regorafenib demonstrated anti-angiogenic activity in a rat tumor model, and inhibition of tumor growth as well as anti-metastatic activity in several mouse xenograft models including some for human colorectal carcinoma.

TargetActionsOrganism
AVascular endothelial growth factor receptor 1
inhibitor
Human
AVascular endothelial growth factor receptor 2
inhibitor
Human
AVascular endothelial growth factor receptor 3
inhibitor
Human
AMast/stem cell growth factor receptor Kit
inhibitor
Human
APlatelet-derived growth factor receptor alpha
inhibitor
Human
APlatelet-derived growth factor receptor beta
inhibitor
Human
AFibroblast growth factor receptor 1
inhibitor
Human
AFibroblast growth factor receptor 2
inhibitor
Human
AAngiopoietin-1 receptor
inhibitor
Human
ADiscoidin domain-containing receptor 2
inhibitor
Human
AHigh affinity nerve growth factor receptor
inhibitor
Human
AEphrin type-A receptor 2
inhibitor
Human
ARAF proto-oncogene serine/threonine-protein kinase
inhibitor
Human
ASerine/threonine-protein kinase B-raf
inhibitor
Human
AMitogen-activated protein kinase 11
inhibitor
Human
ATyrosine-protein kinase FRK
inhibitor
Human
ATyrosine-protein kinase ABL1
inhibitor
Human
AProto-oncogene tyrosine-protein kinase receptor Ret
inhibitor
Human
Absorption

Cmax = 2.5 μg/mL; Tmax = 4 hours; AUC = 70.4 μgh/mL; Cmax, steady-state = 3.9 μg/mL; AUC, steady-state = 58.3 μgh/mL; The mean relative bioavailability of tablets compared to an oral solution is 69% to 83%.

Volume of distribution

Regorafenib undergoes enterohepatic circulation with multiple plasma concentration peaks observed across the 24-hour dosing interval.

Protein binding

Regorafenib is highly bound (99.5%) to human plasma proteins.

Metabolism

Regorafenib is metabolized by CYP3A4 and UGT1A9. The main circulating metabolites of regorafenib measured at steady-state in human plasma are M-2 (N-oxide) and M-5 (N-oxide and N-desmethyl), both of them having similar in vitro pharmacological activity and steady-state concentrations as regorafenib. M-2 and M-5 are highly protein bound (99.8% and 99.95%, respectively).

Route of elimination

Approximately 71% of a radiolabeled dose was excreted in feces (47% as parent compound, 24% as metabolites) and 19% of the dose was excreted in urine (17% as glucuronides) within 12 days after administration of a radiolabeled oral solution at a dose of 120 mg.

Half life

Regorafenib, 160 mg oral dose = 28 hours (14 - 58 hours); M2 metabolite, 160 mg oral dose = 25 hours (14-32 hours); M5 metabolite, 160 mg oral dose = 51 hours (32-72 hours);

Clearance
Not Available
Toxicity

The most common adverse reactions (≥20%) are asthenia/fatigue, HFSR, diarrhea, decreased appetite/food intake, hypertension, mucositis, dysphonia, and infection, pain (not otherwise specified), decreased weight, gastrointestinal and abdominal pain, rash, fever, and nausea

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

Interactions

Drug Interactions
DrugInteractionDrug group
AcebutololRegorafenib may increase the bradycardic activities of Acebutolol.Approved
AcetaminophenThe serum concentration of Acetaminophen can be increased when it is combined with Regorafenib.Approved
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Regorafenib.Approved
AcetyldigoxinAcetyldigoxin may decrease the cardiotoxic activities of Regorafenib.Experimental
Acetylsalicylic acidThe serum concentration of Acetylsalicylic acid can be increased when it is combined with Regorafenib.Approved, Vet Approved
AfatinibThe serum concentration of Afatinib can be increased when it is combined with Regorafenib.Approved
AldosteroneThe serum concentration of Aldosterone can be increased when it is combined with Regorafenib.Experimental, Investigational
AlitretinoinThe serum concentration of Alitretinoin can be increased when it is combined with Regorafenib.Approved, Investigational
AlprenololRegorafenib may increase the bradycardic activities of Alprenolol.Approved, Withdrawn
AmbrisentanThe serum concentration of Ambrisentan can be increased when it is combined with Regorafenib.Approved, Investigational
AmiodaroneThe serum concentration of Regorafenib can be increased when it is combined with Amiodarone.Approved, Investigational
AmitriptylineThe serum concentration of Amitriptyline can be increased when it is combined with Regorafenib.Approved
AmodiaquineThe serum concentration of Amodiaquine can be increased when it is combined with Regorafenib.Approved, Investigational
ApixabanThe serum concentration of Apixaban can be increased when it is combined with Regorafenib.Approved
AprepitantThe serum concentration of Regorafenib can be increased when it is combined with Aprepitant.Approved, Investigational
ArotinololRegorafenib may increase the bradycardic activities of Arotinolol.Approved, Investigational
Arsenic trioxideThe serum concentration of Arsenic trioxide can be increased when it is combined with Regorafenib.Approved, Investigational
AtazanavirThe serum concentration of Regorafenib can be increased when it is combined with Atazanavir.Approved, Investigational
AtenololRegorafenib may increase the bradycardic activities of Atenolol.Approved
AtomoxetineThe metabolism of Regorafenib can be decreased when combined with Atomoxetine.Approved
AtorvastatinThe risk or severity of adverse effects can be increased when Regorafenib is combined with Atorvastatin.Approved
AxitinibThe serum concentration of Axitinib can be increased when it is combined with Regorafenib.Approved, Investigational
BefunololRegorafenib may increase the bradycardic activities of Befunolol.Experimental
BelinostatThe serum concentration of Belinostat can be increased when it is combined with Regorafenib.Approved, Investigational
BetamethasoneThe serum concentration of Betamethasone can be increased when it is combined with Regorafenib.Approved, Vet Approved
BetaxololRegorafenib may increase the bradycardic activities of Betaxolol.Approved
BevacizumabBevacizumab may increase the cardiotoxic activities of Regorafenib.Approved, Investigational
BevantololRegorafenib may increase the bradycardic activities of Bevantolol.Approved
BisoprololRegorafenib may increase the bradycardic activities of Bisoprolol.Approved
BoceprevirThe serum concentration of Regorafenib can be increased when it is combined with Boceprevir.Approved, Withdrawn
BopindololRegorafenib may increase the bradycardic activities of Bopindolol.Approved
BortezomibThe metabolism of Regorafenib can be decreased when combined with Bortezomib.Approved, Investigational
BosentanThe serum concentration of Regorafenib can be decreased when it is combined with Bosentan.Approved, Investigational
BosutinibThe serum concentration of Bosutinib can be increased when it is combined with Regorafenib.Approved
Brentuximab vedotinThe serum concentration of Brentuximab vedotin can be increased when it is combined with Regorafenib.Approved
BromocriptineThe serum concentration of Bromocriptine can be increased when it is combined with Regorafenib.Approved, Investigational
BucindololRegorafenib may increase the bradycardic activities of Bucindolol.Investigational
BufuralolRegorafenib may increase the bradycardic activities of Bufuralol.Experimental, Investigational
BupranololRegorafenib may increase the bradycardic activities of Bupranolol.Approved
CabazitaxelThe risk or severity of adverse effects can be increased when Cabazitaxel is combined with Regorafenib.Approved
CabergolineThe risk or severity of adverse effects can be increased when Cabergoline is combined with Regorafenib.Approved
CaffeineThe serum concentration of Caffeine can be increased when it is combined with Regorafenib.Approved
CamptothecinThe serum concentration of Camptothecin can be increased when it is combined with Regorafenib.Experimental
CanagliflozinThe serum concentration of Canagliflozin can be increased when it is combined with Regorafenib.Approved
CarbamazepineThe serum concentration of Regorafenib can be decreased when it is combined with Carbamazepine.Approved, Investigational
CarfilzomibThe serum concentration of Carfilzomib can be increased when it is combined with Regorafenib.Approved
CarteololRegorafenib may increase the bradycardic activities of Carteolol.Approved
CarvedilolRegorafenib may increase the bradycardic activities of Carvedilol.Approved, Investigational
CeliprololRegorafenib may increase the bradycardic activities of Celiprolol.Approved, Investigational
CerivastatinThe serum concentration of Cerivastatin can be increased when it is combined with Regorafenib.Withdrawn
ChlorpromazineThe serum concentration of Chlorpromazine can be increased when it is combined with Regorafenib.Approved, Vet Approved
CilostazolThe serum concentration of Cilostazol can be increased when it is combined with Regorafenib.Approved
CimetidineThe serum concentration of Cimetidine can be increased when it is combined with Regorafenib.Approved
CiprofloxacinThe serum concentration of Ciprofloxacin can be increased when it is combined with Regorafenib.Approved, Investigational
CisplatinThe serum concentration of Cisplatin can be increased when it is combined with Regorafenib.Approved
CitalopramThe serum concentration of Citalopram can be increased when it is combined with Regorafenib.Approved
ClarithromycinThe serum concentration of Regorafenib can be increased when it is combined with Clarithromycin.Approved
ClemastineThe metabolism of Regorafenib can be decreased when combined with Clemastine.Approved
ClobazamThe serum concentration of Clobazam can be increased when it is combined with Regorafenib.Approved, Illicit
ClomifeneThe serum concentration of Clomifene can be increased when it is combined with Regorafenib.Approved, Investigational
ClonidineThe serum concentration of Clonidine can be increased when it is combined with Regorafenib.Approved
ClopidogrelThe serum concentration of Clopidogrel can be increased when it is combined with Regorafenib.Approved, Nutraceutical
CloranololRegorafenib may increase the bradycardic activities of Cloranolol.Experimental
ClotrimazoleThe metabolism of Regorafenib can be decreased when combined with Clotrimazole.Approved, Vet Approved
ClozapineThe serum concentration of Clozapine can be increased when it is combined with Regorafenib.Approved
CobicistatThe serum concentration of Regorafenib can be increased when it is combined with Cobicistat.Approved
CobimetinibThe serum concentration of Cobimetinib can be increased when it is combined with Regorafenib.Approved
ColchicineThe serum concentration of Colchicine can be increased when it is combined with Regorafenib.Approved
ConivaptanThe serum concentration of Regorafenib can be increased when it is combined with Conivaptan.Approved, Investigational
Conjugated estrogensThe serum concentration of Conjugated estrogens can be increased when it is combined with Regorafenib.Approved
CopanlisibThe serum concentration of Copanlisib can be increased when it is combined with Regorafenib.Approved
CrizotinibThe metabolism of Regorafenib can be decreased when combined with Crizotinib.Approved
CyclophosphamideCyclophosphamide may increase the cardiotoxic activities of Regorafenib.Approved, Investigational
CyclosporineThe metabolism of Regorafenib can be decreased when combined with Cyclosporine.Approved, Investigational, Vet Approved
CymarinCymarin may decrease the cardiotoxic activities of Regorafenib.Experimental
Dabigatran etexilateThe serum concentration of the active metabolites of Dabigatran etexilate can be increased when Dabigatran etexilate is used in combination with Regorafenib.Approved
DabrafenibThe serum concentration of Regorafenib can be decreased when it is combined with Dabrafenib.Approved
DactinomycinThe serum concentration of Dactinomycin can be increased when it is combined with Regorafenib.Approved
DapagliflozinThe serum concentration of Dapagliflozin can be increased when it is combined with Regorafenib.Approved
DarunavirThe serum concentration of Regorafenib can be increased when it is combined with Darunavir.Approved
DasatinibThe serum concentration of Regorafenib can be increased when it is combined with Dasatinib.Approved, Investigational
DaunorubicinThe serum concentration of Daunorubicin can be increased when it is combined with Regorafenib.Approved
DebrisoquinThe serum concentration of Debrisoquin can be increased when it is combined with Regorafenib.Approved, Investigational
DeferasiroxThe serum concentration of Regorafenib can be decreased when it is combined with Deferasirox.Approved, Investigational
DelavirdineThe metabolism of Regorafenib can be decreased when combined with Delavirdine.Approved
DeslanosideDeslanoside may decrease the cardiotoxic activities of Regorafenib.Approved
DexamethasoneThe serum concentration of Dexamethasone can be increased when it is combined with Regorafenib.Approved, Investigational, Vet Approved
DiazepamThe serum concentration of Diazepam can be increased when it is combined with Regorafenib.Approved, Illicit, Vet Approved
DiethylstilbestrolThe serum concentration of Diethylstilbestrol can be increased when it is combined with Regorafenib.Approved, Investigational
DigitoxinDigitoxin may decrease the cardiotoxic activities of Regorafenib.Approved, Investigational
DigoxinRegorafenib may increase the bradycardic activities of Digoxin.Approved
DihydroergocornineThe risk or severity of adverse effects can be increased when Dihydroergocornine is combined with Regorafenib.Approved
DihydroergocristineThe risk or severity of adverse effects can be increased when Dihydroergocristine is combined with Regorafenib.Experimental
DihydroergocryptineThe risk or severity of adverse effects can be increased when Dihydroergocryptine is combined with Regorafenib.Experimental
DihydroergotamineThe metabolism of Regorafenib can be decreased when combined with Dihydroergotamine.Approved
DihydrotestosteroneThe serum concentration of Dihydrotestosterone can be increased when it is combined with Regorafenib.Illicit
DiltiazemRegorafenib may increase the bradycardic activities of Diltiazem.Approved
DipyridamoleThe serum concentration of Dipyridamole can be increased when it is combined with Regorafenib.Approved
DocetaxelThe risk or severity of adverse effects can be increased when Docetaxel is combined with Regorafenib.Approved, Investigational
DomperidoneThe serum concentration of Domperidone can be increased when it is combined with Regorafenib.Approved, Investigational, Vet Approved
DoxorubicinThe serum concentration of Doxorubicin can be increased when it is combined with Regorafenib.Approved, Investigational
DoxycyclineThe metabolism of Regorafenib can be decreased when combined with Doxycycline.Approved, Investigational, Vet Approved
DronedaroneThe metabolism of Regorafenib can be decreased when combined with Dronedarone.Approved
EdoxabanThe serum concentration of Edoxaban can be increased when it is combined with Regorafenib.Approved
ElbasvirThe serum concentration of Elbasvir can be increased when it is combined with Regorafenib.Approved
EletriptanThe serum concentration of Eletriptan can be increased when it is combined with Regorafenib.Approved, Investigational
EnasidenibThe serum concentration of Enasidenib can be increased when it is combined with Regorafenib.Approved
EpanololRegorafenib may increase the bradycardic activities of Epanolol.Experimental
EpinastineThe serum concentration of Epinastine can be increased when it is combined with Regorafenib.Approved, Investigational
ErgonovineThe risk or severity of adverse effects can be increased when Ergonovine is combined with Regorafenib.Approved
ErgotamineThe risk or severity of adverse effects can be increased when Ergotamine is combined with Regorafenib.Approved
ErlotinibThe serum concentration of Erlotinib can be increased when it is combined with Regorafenib.Approved, Investigational
ErythromycinThe metabolism of Regorafenib can be decreased when combined with Erythromycin.Approved, Vet Approved
EsmololRegorafenib may increase the bradycardic activities of Esmolol.Approved
EstradiolThe serum concentration of Estradiol can be increased when it is combined with Regorafenib.Approved, Investigational, Vet Approved
EstriolThe serum concentration of Estriol can be increased when it is combined with Regorafenib.Approved, Investigational, Vet Approved
EstroneThe serum concentration of Estrone can be increased when it is combined with Regorafenib.Approved
Ethinyl EstradiolThe serum concentration of Ethinyl Estradiol can be increased when it is combined with Regorafenib.Approved
EtoposideThe serum concentration of Etoposide can be increased when it is combined with Regorafenib.Approved
EverolimusThe serum concentration of Everolimus can be increased when it is combined with Regorafenib.Approved
EzetimibeThe serum concentration of Ezetimibe can be increased when it is combined with Regorafenib.Approved
FesoterodineThe serum concentration of Fesoterodine can be increased when it is combined with Regorafenib.Approved
FexofenadineThe serum concentration of Fexofenadine can be increased when it is combined with Regorafenib.Approved
FidaxomicinThe serum concentration of Fidaxomicin can be increased when it is combined with Regorafenib.Approved
FluconazoleThe metabolism of Regorafenib can be decreased when combined with Fluconazole.Approved
Fluticasone furoateThe serum concentration of Fluticasone furoate can be increased when it is combined with Regorafenib.Approved
FluvastatinThe serum concentration of Fluvastatin can be increased when it is combined with Regorafenib.Approved
FluvoxamineThe metabolism of Regorafenib can be decreased when combined with Fluvoxamine.Approved, Investigational
FosamprenavirThe metabolism of Regorafenib can be decreased when combined with Fosamprenavir.Approved
FosaprepitantThe serum concentration of Regorafenib can be increased when it is combined with Fosaprepitant.Approved
FosphenytoinThe serum concentration of Regorafenib can be decreased when it is combined with Fosphenytoin.Approved
Fusidic AcidThe serum concentration of Regorafenib can be increased when it is combined with Fusidic Acid.Approved
GefitinibThe serum concentration of Gefitinib can be increased when it is combined with Regorafenib.Approved, Investigational
GemcitabineThe serum concentration of Gemcitabine can be increased when it is combined with Regorafenib.Approved
GitoformateGitoformate may decrease the cardiotoxic activities of Regorafenib.Experimental
GlecaprevirThe serum concentration of Glecaprevir can be increased when it is combined with Regorafenib.Approved
GrazoprevirThe serum concentration of Grazoprevir can be increased when it is combined with Regorafenib.Approved
GrepafloxacinThe serum concentration of Grepafloxacin can be increased when it is combined with Regorafenib.Investigational, Withdrawn
HaloperidolThe serum concentration of Haloperidol can be increased when it is combined with Regorafenib.Approved
HydrocortisoneThe serum concentration of Hydrocortisone can be increased when it is combined with Regorafenib.Approved, Vet Approved
IbuprofenThe serum concentration of Ibuprofen can be increased when it is combined with Regorafenib.Approved
IdelalisibThe serum concentration of Regorafenib can be increased when it is combined with Idelalisib.Approved
ImatinibThe metabolism of Regorafenib can be decreased when combined with Imatinib.Approved
ImipramineThe serum concentration of Imipramine can be increased when it is combined with Regorafenib.Approved
IndacaterolThe serum concentration of Indacaterol can be increased when it is combined with Regorafenib.Approved
IndenololRegorafenib may increase the bradycardic activities of Indenolol.Withdrawn
IndinavirThe serum concentration of Regorafenib can be increased when it is combined with Indinavir.Approved
IndomethacinThe serum concentration of Indomethacin can be increased when it is combined with Regorafenib.Approved, Investigational
Inotuzumab ozogamicinThe serum concentration of Inotuzumab ozogamicin can be increased when it is combined with Regorafenib.Approved
IrinotecanThe serum concentration of the active metabolites of Irinotecan can be increased when Irinotecan is used in combination with Regorafenib.Approved, Investigational
IsavuconazoniumThe metabolism of Regorafenib can be decreased when combined with Isavuconazonium.Approved, Investigational
IsradipineThe metabolism of Regorafenib can be decreased when combined with Isradipine.Approved
ItraconazoleThe serum concentration of Regorafenib can be increased when it is combined with Itraconazole.Approved, Investigational
IvabradineRegorafenib may increase the bradycardic activities of Ivabradine.Approved
IvacaftorThe serum concentration of Regorafenib can be increased when it is combined with Ivacaftor.Approved
IvermectinThe serum concentration of Ivermectin can be increased when it is combined with Regorafenib.Approved, Vet Approved
KetazolamThe serum concentration of Ketazolam can be increased when it is combined with Regorafenib.Approved
KetoconazoleThe serum concentration of Regorafenib can be increased when it is combined with Ketoconazole.Approved, Investigational
LabetalolRegorafenib may increase the bradycardic activities of Labetalol.Approved
LamivudineThe serum concentration of Lamivudine can be increased when it is combined with Regorafenib.Approved, Investigational
LamotrigineThe serum concentration of Lamotrigine can be increased when it is combined with Regorafenib.Approved, Investigational
Lanatoside CLanatoside C may decrease the cardiotoxic activities of Regorafenib.Experimental
LandiololRegorafenib may increase the bradycardic activities of Landiolol.Investigational
LansoprazoleThe serum concentration of Lansoprazole can be increased when it is combined with Regorafenib.Approved, Investigational
LedipasvirThe serum concentration of Ledipasvir can be increased when it is combined with Regorafenib.Approved
LenalidomideThe serum concentration of Lenalidomide can be increased when it is combined with Regorafenib.Approved
LenvatinibThe serum concentration of Lenvatinib can be increased when it is combined with Regorafenib.Approved
LevetiracetamThe serum concentration of Levetiracetam can be increased when it is combined with Regorafenib.Approved, Investigational
LevobunololRegorafenib may increase the bradycardic activities of Levobunolol.Approved
LevofloxacinThe serum concentration of Levofloxacin can be increased when it is combined with Regorafenib.Approved, Investigational
LevomilnacipranThe serum concentration of Levomilnacipran can be increased when it is combined with Regorafenib.Approved
LinagliptinThe serum concentration of Linagliptin can be increased when it is combined with Regorafenib.Approved
LisurideThe risk or severity of adverse effects can be increased when Lisuride is combined with Regorafenib.Approved, Investigational
LoperamideThe serum concentration of Loperamide can be increased when it is combined with Regorafenib.Approved
LopinavirThe serum concentration of Regorafenib can be increased when it is combined with Lopinavir.Approved
LosartanThe serum concentration of Losartan can be increased when it is combined with Regorafenib.Approved
LovastatinThe metabolism of Regorafenib can be decreased when combined with Lovastatin.Approved, Investigational
LuliconazoleThe serum concentration of Regorafenib can be increased when it is combined with Luliconazole.Approved
LumacaftorThe serum concentration of Regorafenib can be decreased when it is combined with Lumacaftor.Approved
Lysergic Acid DiethylamideThe risk or severity of adverse effects can be increased when Lysergic Acid Diethylamide is combined with Regorafenib.Illicit, Investigational, Withdrawn
MannitolThe serum concentration of Mannitol can be increased when it is combined with Regorafenib.Approved, Investigational
MepindololRegorafenib may increase the bradycardic activities of Mepindolol.Experimental
MetergolineThe risk or severity of adverse effects can be increased when Metergoline is combined with Regorafenib.Experimental
MethotrexateThe serum concentration of Methotrexate can be increased when it is combined with Regorafenib.Approved
MethylergometrineThe risk or severity of adverse effects can be increased when Methylergometrine is combined with Regorafenib.Approved
MethylprednisoloneThe serum concentration of Methylprednisolone can be increased when it is combined with Regorafenib.Approved, Vet Approved
MethysergideThe risk or severity of adverse effects can be increased when Methysergide is combined with Regorafenib.Approved
MetildigoxinMetildigoxin may decrease the cardiotoxic activities of Regorafenib.Experimental
MetipranololRegorafenib may increase the bradycardic activities of Metipranolol.Approved
MetoprololRegorafenib may increase the bradycardic activities of Metoprolol.Approved, Investigational
MevastatinThe serum concentration of Mevastatin can be increased when it is combined with Regorafenib.Experimental
MidazolamThe serum concentration of Midazolam can be increased when it is combined with Regorafenib.Approved, Illicit
MifepristoneThe serum concentration of Regorafenib can be increased when it is combined with Mifepristone.Approved, Investigational
MirabegronThe serum concentration of Mirabegron can be increased when it is combined with Regorafenib.Approved
MitoxantroneThe serum concentration of Mitoxantrone can be increased when it is combined with Regorafenib.Approved, Investigational
MorphineThe serum concentration of Morphine can be increased when it is combined with Regorafenib.Approved, Investigational
Mycophenolate mofetilThe serum concentration of Mycophenolate mofetil can be increased when it is combined with Regorafenib.Approved, Investigational
NadololRegorafenib may increase the bradycardic activities of Nadolol.Approved
NaloxegolThe serum concentration of Naloxegol can be increased when it is combined with Regorafenib.Approved
NaloxoneThe serum concentration of Naloxone can be increased when it is combined with Regorafenib.Approved, Vet Approved
NefazodoneThe serum concentration of Regorafenib can be increased when it is combined with Nefazodone.Approved, Withdrawn
NelfinavirThe serum concentration of Regorafenib can be increased when it is combined with Nelfinavir.Approved
NetupitantThe serum concentration of Regorafenib can be increased when it is combined with Netupitant.Approved
NevirapineThe serum concentration of Regorafenib can be decreased when it is combined with Nevirapine.Approved
NicardipineThe serum concentration of Nicardipine can be increased when it is combined with Regorafenib.Approved
NicergolineThe risk or severity of adverse effects can be increased when Nicergoline is combined with Regorafenib.Approved, Investigational
NifedipineThe serum concentration of Nifedipine can be increased when it is combined with Regorafenib.Approved
NilotinibThe metabolism of Regorafenib can be decreased when combined with Nilotinib.Approved, Investigational
NintedanibThe serum concentration of Nintedanib can be increased when it is combined with Regorafenib.Approved
NizatidineThe serum concentration of Nizatidine can be increased when it is combined with Regorafenib.Approved
OdanacatibThe serum concentration of Odanacatib can be increased when it is combined with Regorafenib.Investigational
OlanzapineThe serum concentration of Olanzapine can be increased when it is combined with Regorafenib.Approved, Investigational
OlaparibThe metabolism of Regorafenib can be decreased when combined with Olaparib.Approved
OleandrinOleandrin may decrease the cardiotoxic activities of Regorafenib.Experimental, Investigational
OmbitasvirThe serum concentration of Ombitasvir can be increased when it is combined with Regorafenib.Approved
OsimertinibThe serum concentration of Regorafenib can be increased when it is combined with Osimertinib.Approved
OuabainOuabain may decrease the cardiotoxic activities of Regorafenib.Approved
OxprenololRegorafenib may increase the bradycardic activities of Oxprenolol.Approved
PaclitaxelThe risk or severity of adverse effects can be increased when Paclitaxel is combined with Regorafenib.Approved, Vet Approved
PalbociclibThe serum concentration of Regorafenib can be increased when it is combined with Palbociclib.Approved
PanobinostatThe serum concentration of Panobinostat can be increased when it is combined with Regorafenib.Approved, Investigational
PazopanibThe serum concentration of Pazopanib can be increased when it is combined with Regorafenib.Approved
PenbutololRegorafenib may increase the bradycardic activities of Penbutolol.Approved, Investigational
PentobarbitalThe serum concentration of Regorafenib can be decreased when it is combined with Pentobarbital.Approved, Vet Approved
PergolideThe risk or severity of adverse effects can be increased when Pergolide is combined with Regorafenib.Approved, Investigational, Vet Approved, Withdrawn
PeruvosidePeruvoside may decrease the cardiotoxic activities of Regorafenib.Experimental
PhenobarbitalThe serum concentration of Regorafenib can be decreased when it is combined with Phenobarbital.Approved
PhenytoinThe serum concentration of Regorafenib can be decreased when it is combined with Phenytoin.Approved, Vet Approved
PibrentasvirThe serum concentration of Pibrentasvir can be increased when it is combined with Regorafenib.Approved
PindololRegorafenib may increase the bradycardic activities of Pindolol.Approved
PitavastatinThe serum concentration of Pitavastatin can be increased when it is combined with Regorafenib.Approved
PomalidomideThe serum concentration of Pomalidomide can be increased when it is combined with Regorafenib.Approved
PonatinibThe serum concentration of Ponatinib can be increased when it is combined with Regorafenib.Approved
PosaconazoleThe serum concentration of Regorafenib can be increased when it is combined with Posaconazole.Approved, Investigational, Vet Approved
PractololRegorafenib may increase the bradycardic activities of Practolol.Approved
PravastatinThe serum concentration of Pravastatin can be increased when it is combined with Regorafenib.Approved
PrazosinThe serum concentration of Prazosin can be increased when it is combined with Regorafenib.Approved
PrednisoloneThe serum concentration of Prednisolone can be increased when it is combined with Regorafenib.Approved, Vet Approved
PrednisoneThe serum concentration of Prednisone can be increased when it is combined with Regorafenib.Approved, Vet Approved
PrimidoneThe serum concentration of Regorafenib can be decreased when it is combined with Primidone.Approved, Vet Approved
ProgesteroneThe serum concentration of Progesterone can be increased when it is combined with Regorafenib.Approved, Vet Approved
PropranololRegorafenib may increase the bradycardic activities of Propranolol.Approved, Investigational
ProscillaridinProscillaridin may decrease the cardiotoxic activities of Regorafenib.Experimental
PrucaloprideThe serum concentration of Prucalopride can be increased when it is combined with Regorafenib.Approved
QuetiapineThe serum concentration of Quetiapine can be increased when it is combined with Regorafenib.Approved
QuinidineThe serum concentration of Quinidine can be increased when it is combined with Regorafenib.Approved
QuinineThe serum concentration of Quinine can be increased when it is combined with Regorafenib.Approved
RanitidineThe serum concentration of Ranitidine can be increased when it is combined with Regorafenib.Approved
RanolazineThe serum concentration of Ranolazine can be increased when it is combined with Regorafenib.Approved, Investigational
ReserpineThe serum concentration of Reserpine can be increased when it is combined with Regorafenib.Approved, Investigational
RifabutinThe serum concentration of Regorafenib can be decreased when it is combined with Rifabutin.Approved
RifampicinThe serum concentration of Regorafenib can be decreased when it is combined with Rifampicin.Approved
RifapentineThe serum concentration of Regorafenib can be decreased when it is combined with Rifapentine.Approved
RifaximinThe serum concentration of Rifaximin can be increased when it is combined with Regorafenib.Approved, Investigational
RisperidoneThe serum concentration of Risperidone can be increased when it is combined with Regorafenib.Approved, Investigational
RitonavirThe serum concentration of Regorafenib can be increased when it is combined with Ritonavir.Approved, Investigational
RivaroxabanThe serum concentration of Rivaroxaban can be increased when it is combined with Regorafenib.Approved
RomidepsinThe serum concentration of Romidepsin can be increased when it is combined with Regorafenib.Approved, Investigational
RosuvastatinThe serum concentration of Rosuvastatin can be increased when it is combined with Regorafenib.Approved
Salicylic acidThe serum concentration of Salicylic acid can be increased when it is combined with Regorafenib.Approved, Vet Approved
SaquinavirThe serum concentration of Regorafenib can be increased when it is combined with Saquinavir.Approved, Investigational
SelexipagThe serum concentration of Selexipag can be increased when it is combined with Regorafenib.Approved
SildenafilThe metabolism of Regorafenib can be decreased when combined with Sildenafil.Approved, Investigational
SilodosinThe serum concentration of Silodosin can be increased when it is combined with Regorafenib.Approved
SiltuximabThe serum concentration of Regorafenib can be decreased when it is combined with Siltuximab.Approved
SimeprevirThe serum concentration of Regorafenib can be increased when it is combined with Simeprevir.Approved
SimvastatinThe serum concentration of Simvastatin can be increased when it is combined with Regorafenib.Approved
SitagliptinThe serum concentration of Sitagliptin can be increased when it is combined with Regorafenib.Approved, Investigational
SofosbuvirThe serum concentration of Sofosbuvir can be increased when it is combined with Regorafenib.Approved
SorafenibThe serum concentration of Sorafenib can be increased when it is combined with Regorafenib.Approved, Investigational
SotalolRegorafenib may increase the bradycardic activities of Sotalol.Approved
SparfloxacinThe serum concentration of Sparfloxacin can be increased when it is combined with Regorafenib.Approved, Investigational
SphingosineThe serum concentration of Sphingosine can be increased when it is combined with Regorafenib.Experimental
St. John's WortThe serum concentration of Regorafenib can be decreased when it is combined with St. John's Wort.Investigational, Nutraceutical
StiripentolThe serum concentration of Regorafenib can be increased when it is combined with Stiripentol.Approved
SulfisoxazoleThe metabolism of Regorafenib can be decreased when combined with Sulfisoxazole.Approved, Vet Approved
TacrolimusThe serum concentration of Tacrolimus can be increased when it is combined with Regorafenib.Approved, Investigational
TalinololRegorafenib may increase the bradycardic activities of Talinolol.Investigational
TamoxifenThe serum concentration of Tamoxifen can be increased when it is combined with Regorafenib.Approved
Taurocholic AcidThe serum concentration of Taurocholic Acid can be increased when it is combined with Regorafenib.Experimental
Technetium Tc-99m sestamibiThe serum concentration of Technetium Tc-99m sestamibi can be increased when it is combined with Regorafenib.Approved
TelaprevirThe serum concentration of Regorafenib can be increased when it is combined with Telaprevir.Approved, Withdrawn
TelithromycinThe serum concentration of Regorafenib can be increased when it is combined with Telithromycin.Approved
TemsirolimusThe serum concentration of Temsirolimus can be increased when it is combined with Regorafenib.Approved
TergurideThe risk or severity of adverse effects can be increased when Terguride is combined with Regorafenib.Experimental
TertatololRegorafenib may increase the bradycardic activities of Tertatolol.Experimental
TicagrelorThe serum concentration of Ticagrelor can be increased when it is combined with Regorafenib.Approved
TiclopidineThe metabolism of Regorafenib can be decreased when combined with Ticlopidine.Approved
TimololRegorafenib may increase the bradycardic activities of Timolol.Approved
TocilizumabThe serum concentration of Regorafenib can be decreased when it is combined with Tocilizumab.Approved
TolvaptanThe serum concentration of Tolvaptan can be increased when it is combined with Regorafenib.Approved
ToremifeneThe serum concentration of Toremifene can be increased when it is combined with Regorafenib.Approved, Investigational
TrastuzumabTrastuzumab may increase the cardiotoxic activities of Regorafenib.Approved, Investigational
Trastuzumab emtansineThe serum concentration of Trastuzumab emtansine can be increased when it is combined with Regorafenib.Approved
UbidecarenoneThe serum concentration of Ubidecarenone can be increased when it is combined with Regorafenib.Approved, Experimental
UlipristalThe serum concentration of Ulipristal can be increased when it is combined with Regorafenib.Approved
UmeclidiniumThe serum concentration of Umeclidinium can be increased when it is combined with Regorafenib.Approved
VecuroniumThe serum concentration of Vecuronium can be increased when it is combined with Regorafenib.Approved
VelpatasvirThe serum concentration of Velpatasvir can be increased when it is combined with Regorafenib.Approved
VenetoclaxThe serum concentration of Venetoclax can be increased when it is combined with Regorafenib.Approved
VenlafaxineThe metabolism of Regorafenib can be decreased when combined with Venlafaxine.Approved
VerapamilRegorafenib may increase the bradycardic activities of Verapamil.Approved
VinblastineThe serum concentration of Vinblastine can be increased when it is combined with Regorafenib.Approved
VincristineThe serum concentration of Vincristine can be increased when it is combined with Regorafenib.Approved, Investigational
VismodegibThe serum concentration of Vismodegib can be increased when it is combined with Regorafenib.Approved
VoriconazoleThe serum concentration of Regorafenib can be increased when it is combined with Voriconazole.Approved, Investigational
VoxilaprevirThe serum concentration of Voxilaprevir can be increased when it is combined with Regorafenib.Approved
WarfarinThe risk or severity of adverse effects can be increased when Warfarin is combined with Regorafenib.Approved
ZidovudineThe serum concentration of Zidovudine can be increased when it is combined with Regorafenib.Approved
ZiprasidoneThe metabolism of Regorafenib can be decreased when combined with Ziprasidone.Approved
Food Interactions
  • When taken with a high-fat meal, AUC increased by 48% and decreased mean AUC of M2 and M5 metabolites by 20% and 51% respectively.

References

General References
Not Available
External Links
KEGG Drug
D10138
PubChem Compound
11167602
PubChem Substance
175427139
ChemSpider
9342697
BindingDB
50363397
ChEBI
68647
ChEMBL
CHEMBL1946170
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Regorafenib
ATC Codes
L01XE21 — Regorafenib
AHFS Codes
  • 10:00.00 — Antineoplastic Agents
FDA label
Download (457 KB)
MSDS
Download (479 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1Active Not RecruitingOtherPediatric Oncology1
1Active Not RecruitingTreatmentAdvanced Cancers1
1Active Not RecruitingTreatmentGastrointestinal Stromal Tumors1
1Active Not RecruitingTreatmentNeoplasms3
1CompletedNot AvailableNeoplasms2
1CompletedScreeningDietary Fats / Pharmacokinetics1
1CompletedTreatmentColorectal Cancers1
1CompletedTreatmentNeoplasms3
1CompletedTreatmentNeoplasms, Colorectal1
1CompletedTreatmentOncology1
1CompletedTreatmentTumors1
1Not Yet RecruitingTreatmentLeukemia Acute Myeloid Leukemia (AML)1
1Not Yet RecruitingTreatmentLocally Advanced Solid Malignancies / Metastatic Solid Malignancies1
1RecruitingTreatmentMetastatic Colorectal Cancers1
1RecruitingTreatmentPretreated Metastatic Colorectal Cancer1
1RecruitingTreatmentRectal Carcinoma1
1RecruitingTreatmentTumors, Solid1
1TerminatedTreatmentKRAS and NRAS Wild-type Colorectal Cancer1
1TerminatedTreatmentNeoplasms1
1, 2Active Not RecruitingTreatmentAdvanced Gastrointestinal Cancers1
1, 2Not Yet RecruitingTreatmentColorectal Cancers1
1, 2RecruitingTreatmentDigestive Cancers1
1, 2RecruitingTreatmentNeoplasms Metastasis / Neoplasms, Esophageal / Stomach Neoplasms1
1, 2RecruitingTreatmentPreviously Treated Metastatic Colorectal Cancer1
2Active Not RecruitingBasic ScienceMalignant Neoplasm of Colon1
2Active Not RecruitingSupportive CareMalignant Neoplasms of Independent (Primary) Multiple Sites / Metastatic Colorectal Cancers1
2Active Not RecruitingTreatmentAdenocarcinoma of the Colon / Adenocarcinoma of the Rectum / Neoplasms, Colorectal1
2Active Not RecruitingTreatmentAdvanced Chemorefractory Colorectal Adenocarcinoma1
2Active Not RecruitingTreatmentCancer of the Bile Duct1
2Active Not RecruitingTreatmentCarcinoma, Adenoid Cystic1
2Active Not RecruitingTreatmentColon Adenocarcinoma / Rectal Adenocarcinoma / Stage III Colorectal Cancer / Stage IIIA Colorectal Cancer / Stage IIIB Colorectal Cancer / Stage IIIC Colorectal Cancer / Stage IV Colorectal Cancer / Stage IVA Colorectal Cancer / Stage IVB Colorectal Cancer1
2Active Not RecruitingTreatmentEsophageal Cancers / Malignant Neoplasm of Stomach1
2Active Not RecruitingTreatmentGastrointestinal Stromal Tumors1
2Active Not RecruitingTreatmentGlioblastoma Multiforme1
2Active Not RecruitingTreatmentMalignant Neoplasm of Pancreas1
2Active Not RecruitingTreatmentMelanoma1
2Active Not RecruitingTreatmentMetastatic Biliary Tract Carcinoma1
2Active Not RecruitingTreatmentMetastatic Colorectal Cancers3
2Active Not RecruitingTreatmentNeoplasms, Colorectal3
2Active Not RecruitingTreatmentPancreatic Adenocarcinoma Metastatic1
2Active Not RecruitingTreatmentRenal Cell Adenocarcinoma1
2Active Not RecruitingTreatmentSarcomas1
2CompletedTreatmentAdenocarcinomas of the Gastroesophageal Junction / Node Positive Esophogeal Cancer / Stage IIB Esophageal Adenocarcinoma / Stage IIIA Esophageal Adenocarcinoma / Stage IIIB Esophageal Adenocarcinoma / Stage IIIC Esophageal Adenocarcinoma1
2CompletedTreatmentMetastatic Disease / Neoplasms, Colorectal1
2CompletedTreatmentNeoplasms, Colorectal1
2Enrolling by InvitationTreatmentBreastcancer / Colorectal Cancers / Lung Cancer Non-Small Cell Cancer (NSCLC) / Malignant Neoplasm of Pancreas1
2Not Yet RecruitingTreatmentColorectal Cancers1
2RecruitingNot AvailableMetastatic Colorectal Cancers1
2RecruitingTreatmentAdult Angiosarcoma / Recurrent Adult Soft Tissue Sarcoma / Stage III Adult Soft Tissue Sarcoma / Stage IV Adult Soft Tissue Sarcoma1
2RecruitingTreatmentAdvanced Colorectal Cancer1
2RecruitingTreatmentAdvanced Solid Tumors / Multiple Myeloma (MM) / Non-Hodgkin's Lymphoma (NHL)1
2RecruitingTreatmentCancer, Ovarian / Malignant Neoplasm of Pancreas / Melanoma / Sarcomas1
2RecruitingTreatmentCancers / Neoplasia / Neoplasms / Tumors1
2RecruitingTreatmentChondroma / Chondrosarcomas / Ewing Sarcomas / Sarcoma, Osteogenic1
2RecruitingTreatmentColorectal Adenocarcinoma1
2RecruitingTreatmentColorectal Cancers1
2RecruitingTreatmentColorectal Cancers / Palliative Care / Palliative Medicine / Supportive Care1
2RecruitingTreatmentEwing/Ewing-like Sarcoma / Liposarcoma / Sarcoma, Osteogenic1
2RecruitingTreatmentGastrinoma / Glucagonoma / Insulinoma / Metastatic Gastrointestinal Carcinoid Tumor / Pancreatic Polypeptide Tumor / Pulmonary Carcinoid Tumor / Recurrent Gastrointestinal Carcinoid Tumor / Recurrent Islet Cell Carcinoma / Somatostatinoma1
2RecruitingTreatmentGastrointestinal Carcinoma, Non-colon / Non-Small Cell Lung Carcinoma (NSCLC) / Transitional Cell Carcinoma / Upper Aerodigestive Tract Carcinoma1
2RecruitingTreatmentGastrointestinal Stromal Tumors1
2RecruitingTreatmentGastrointestinal Stromal Tumors (GISTs)1
2RecruitingTreatmentGastrointestinal Stromal Tumour (GIST)1
2RecruitingTreatmentGastrointestinal Stromal Tumours1
2RecruitingTreatmentMelanoma1
2RecruitingTreatmentMetastatic Colorectal Adenocarcinoma1
2RecruitingTreatmentMetastatic Colorectal Cancers4
2RecruitingTreatmentNeoplasms, Ovarian1
2RecruitingTreatmentOvarian Carcinoma1
2RecruitingTreatmentThyroid Cancers1
2RecruitingTreatmentUrothelial Cancer (Urinary Bladder, Ureters, or Renal Pelvis Cancer)1
2TerminatedTreatmentCancer, Ovarian / Fallopian Tube Cancer / Primary Peritoneal Cancer1
2TerminatedTreatmentMacular Degeneration1
2TerminatedTreatmentMetastatic Disease / Neoplasms, Colorectal1
2TerminatedTreatmentUpper GI Cancer1
2Unknown StatusTreatmentCholangiocarcinomas1
2Unknown StatusTreatmentRectal Carcinoma1
2WithdrawnTreatmentRectal Adenocarcinoma / Stage IIA Rectal Cancer / Stage IIB Rectal Cancer / Stage IIC Rectal Cancer / Stage IIIA Rectal Cancer / Stage IIIB Rectal Cancer1
2, 3Unknown StatusTreatmentAsian Colorectal Cancer Patients1
3Active Not RecruitingTreatmentColorectal Cancers1
3Active Not RecruitingTreatmentGastrointestinal Stromal Tumors1
3Active Not RecruitingTreatmentHepatocellular,Carcinoma1
3Active Not RecruitingTreatmentNeoplasms, Colorectal1
3CompletedTreatmentMetastatic Colorectal Cancers1
3CompletedTreatmentNeoplasms, Colorectal1
3No Longer AvailableNot AvailableGastrointestinal Stromal Tumors1
3Not Yet RecruitingTreatmentGastro-oesophageal Cancer1
3RecruitingTreatmentMetastatic Colorectal Cancers1
3RecruitingTreatmentStage III (IIIB or IIIC) Colon Cancer1
3TerminatedTreatmentNeoplasms, Colorectal1
3WithdrawnTreatmentMetastatic Colorectal Cancers1
4TerminatedSupportive CarePhysician Education1
Not AvailableActive Not RecruitingNot AvailableNeoplasms1
Not AvailableActive Not RecruitingScreeningMetastatic Colorectal Cancers1
Not AvailableCompletedNot AvailableMetastatic Colorectal Cancers1
Not AvailableCompletedNot AvailableNeoplasms, Colorectal3
Not AvailableNo Longer AvailableNot AvailableGastrointestinal Stromal Tumors1
Not AvailableNo Longer AvailableNot AvailableNeoplasms, Colorectal1
Not AvailableRecruitingNot AvailableGastrointestinal Stromal Tumors1
Not AvailableRecruitingNot AvailableNeoplasms, Colorectal1
Not AvailableRecruitingNot AvailableNeoplasms, Hepatic1
Not AvailableRecruitingDiagnosticColorectal Cancers1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
TabletOral40 mg
Tablet, film coatedOral40 mg
Tablet, film coatedOral40 mg/1
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
CA2315715No2010-06-222018-12-22Canada
CA2526636No2012-10-022024-05-19Canada
CA2549558No2010-08-312020-01-12Canada
US7351834No2000-01-122020-01-12Us
US8680124No2010-06-022030-06-02Us
US8637553No2011-02-162031-02-16Us
US9458107No2011-04-082031-04-08Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubilityInsoluble FDA label
Predicted Properties
PropertyValueSource
Water Solubility0.00102 mg/mLALOGPS
logP4.53ALOGPS
logP4.49ChemAxon
logS-5.7ALOGPS
pKa (Strongest Acidic)10.52ChemAxon
pKa (Strongest Basic)2.02ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area92.35 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity114.73 m3·mol-1ChemAxon
Polarizability41.23 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9649
Blood Brain Barrier+0.851
Caco-2 permeable-0.5138
P-glycoprotein substrateNon-substrate0.5086
P-glycoprotein inhibitor INon-inhibitor0.7141
P-glycoprotein inhibitor IINon-inhibitor0.9359
Renal organic cation transporterNon-inhibitor0.8938
CYP450 2C9 substrateNon-substrate0.6569
CYP450 2D6 substrateNon-substrate0.8212
CYP450 3A4 substrateNon-substrate0.5341
CYP450 1A2 substrateInhibitor0.6168
CYP450 2C9 inhibitorNon-inhibitor0.6171
CYP450 2D6 inhibitorNon-inhibitor0.9145
CYP450 2C19 inhibitorInhibitor0.637
CYP450 3A4 inhibitorNon-inhibitor0.7339
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.6629
Ames testNon AMES toxic0.8143
CarcinogenicityNon-carcinogens0.8684
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.7885 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9488
hERG inhibition (predictor II)Non-inhibitor0.6415
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

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
MS/MS Spectrum - , positiveLC-MS/MSsplash10-001i-0130900000-7cfbbe70d59d3990bb46

Taxonomy

Description
This compound belongs to the class of organic compounds known as diarylethers. These are organic compounds containing the dialkyl ether functional group, with the formula ROR', where R and R' are aryl groups.
Kingdom
Organic compounds
Super Class
Organic oxygen compounds
Class
Organooxygen compounds
Sub Class
Ethers
Direct Parent
Diarylethers
Alternative Parents
Trifluoromethylbenzenes / N-phenylureas / Pyridinecarboxamides / Phenoxy compounds / Phenol ethers / 2-heteroaryl carboxamides / Chlorobenzenes / Fluorobenzenes / Aryl chlorides / Aryl fluorides
show 12 more
Substituents
Diaryl ether / N-phenylurea / Trifluoromethylbenzene / Pyridinecarboxamide / Pyridine carboxylic acid or derivatives / 2-heteroaryl carboxamide / Phenoxy compound / Phenol ether / Halobenzene / Fluorobenzene
show 27 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
aromatic ether, ureas, monochlorobenzenes, monofluorobenzenes, (trifluoromethyl)benzenes, pyridinecarboxamide (CHEBI:68647)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Vegf-b-activated receptor activity
Specific Function
Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFB and PGF, and plays an essential role in the development of embryonic vasculature, the regulation of angiogenesis, cell ...
Gene Name
FLT1
Uniprot ID
P17948
Uniprot Name
Vascular endothelial growth factor receptor 1
Molecular Weight
150767.185 Da
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
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
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Vascular endothelial growth factor-activated receptor activity
Specific Function
Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFC and VEGFD, and plays an essential role in adult lymphangiogenesis and in the development of the vascular network and the cardi...
Gene Name
FLT4
Uniprot ID
P35916
Uniprot Name
Vascular endothelial growth factor receptor 3
Molecular Weight
152755.94 Da
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
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
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
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
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
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
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Protein tyrosine kinase activity
Specific Function
Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of embryonic development, cell proliferation, differentiation ...
Gene Name
FGFR1
Uniprot ID
P11362
Uniprot Name
Fibroblast growth factor receptor 1
Molecular Weight
91866.935 Da
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Protein tyrosine kinase activity
Specific Function
Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of cell proliferation, differentiation, migration and apoptosi...
Gene Name
FGFR2
Uniprot ID
P21802
Uniprot Name
Fibroblast growth factor receptor 2
Molecular Weight
92024.29 Da
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Transmembrane receptor protein tyrosine kinase activity
Specific Function
Tyrosine-protein kinase that acts as cell-surface receptor for ANGPT1, ANGPT2 and ANGPT4 and regulates angiogenesis, endothelial cell survival, proliferation, migration, adhesion and cell spreading...
Gene Name
TEK
Uniprot ID
Q02763
Uniprot Name
Angiopoietin-1 receptor
Molecular Weight
125829.005 Da
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Transmembrane receptor protein tyrosine kinase activity
Specific Function
Tyrosine kinase that functions as cell surface receptor for fibrillar collagen and regulates cell differentiation, remodeling of the extracellular matrix, cell migration and cell proliferation. Req...
Gene Name
DDR2
Uniprot ID
Q16832
Uniprot Name
Discoidin domain-containing receptor 2
Molecular Weight
96735.44 Da
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Transmembrane receptor protein tyrosine kinase activity
Specific Function
Receptor tyrosine kinase involved in the development and the maturation of the central and peripheral nervous systems through regulation of proliferation, differentiation and survival of sympatheti...
Gene Name
NTRK1
Uniprot ID
P04629
Uniprot Name
High affinity nerve growth factor receptor
Molecular Weight
87496.465 Da
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Transmembrane receptor protein tyrosine kinase activity
Specific Function
Receptor tyrosine kinase which binds promiscuously membrane-bound ephrin-A family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. Th...
Gene Name
EPHA2
Uniprot ID
P29317
Uniprot Name
Ephrin type-A receptor 2
Molecular Weight
108265.585 Da
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Protein serine/threonine kinase activity
Specific Function
Serine/threonine-protein kinase that acts as a regulatory link between the membrane-associated Ras GTPases and the MAPK/ERK cascade, and this critical regulatory link functions as a switch determin...
Gene Name
RAF1
Uniprot ID
P04049
Uniprot Name
RAF proto-oncogene serine/threonine-protein kinase
Molecular Weight
73051.025 Da
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Protein serine/threonine kinase activity
Specific Function
Protein kinase involved in the transduction of mitogenic signals from the cell membrane to the nucleus. May play a role in the postsynaptic responses of hippocampal neuron. Phosphorylates MAP2K1, a...
Gene Name
BRAF
Uniprot ID
P15056
Uniprot Name
Serine/threonine-protein kinase B-raf
Molecular Weight
84436.135 Da
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Protein serine/threonine kinase activity
Specific Function
Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK11 is one of the four p38 MAPKs which play an important role in the cascades of cellu...
Gene Name
MAPK11
Uniprot ID
Q15759
Uniprot Name
Mitogen-activated protein kinase 11
Molecular Weight
41356.875 Da
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Receptor binding
Specific Function
Non-receptor tyrosine-protein kinase that negatively regulates cell proliferation. Positively regulates PTEN protein stability through phosphorylation of PTEN on 'Tyr-336', which in turn prevents i...
Gene Name
FRK
Uniprot ID
P42685
Uniprot Name
Tyrosine-protein kinase FRK
Molecular Weight
58253.61 Da
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Syntaxin binding
Specific Function
Non-receptor tyrosine-protein kinase that plays a role in many key processes linked to cell growth and survival such as cytoskeleton remodeling in response to extracellular stimuli, cell motility a...
Gene Name
ABL1
Uniprot ID
P00519
Uniprot Name
Tyrosine-protein kinase ABL1
Molecular Weight
122871.435 Da
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Transmembrane receptor protein tyrosine kinase activity
Specific Function
Receptor tyrosine-protein kinase involved in numerous cellular mechanisms including cell proliferation, neuronal navigation, cell migration, and cell differentiation upon binding with glial cell de...
Gene Name
RET
Uniprot ID
P07949
Uniprot Name
Proto-oncogene tyrosine-protein kinase receptor Ret
Molecular Weight
124317.465 Da

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
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
Substrate
Inhibitor
General Function
Retinoic acid binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform has specificity for phenols. Isoform 2 lacks trans...
Gene Name
UGT1A9
Uniprot ID
O60656
Uniprot Name
UDP-glucuronosyltransferase 1-9
Molecular Weight
59940.495 Da
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
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
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
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
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
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
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
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
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the...
Gene Name
UGT1A1
Uniprot ID
P22309
Uniprot Name
UDP-glucuronosyltransferase 1-1
Molecular Weight
59590.91 Da

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Xenobiotic-transporting atpase activity
Specific Function
High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both fro...
Gene Name
ABCG2
Uniprot ID
Q9UNQ0
Uniprot Name
ATP-binding cassette sub-family G member 2
Molecular Weight
72313.47 Da

Drug created on June 03, 2013 16:30 / Updated on November 14, 2017 08:12