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Identification
NameCobimetinib
Accession NumberDB05239
TypeSmall Molecule
GroupsApproved
DescriptionCobimetinib is an orally active, potent and highly selective small molecule inhibiting mitogen-activated protein kinase kinase 1 (MAP2K1 or MEK1), and central components of the RAS/RAF/MEK/ERK signal transduction pathway. It has been approved in Switzerland and the US, in combination with vemurafenib for the treatment of patients with unresectable or metastatic BRAF V600 mutation-positive melanoma.
Structure
Thumb
SynonymsNot Available
External Identifiers
  • XL-518
  • GDC 0973
  • GDC-0973
  • GDC0973
  • RG 7420
  • RG-7420
  • RG7420
  • RO5514041
  • XL 518
  • XL518
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Cotellictablet, film coated20 mg/1oralGenentech, Inc.2015-11-10Not applicableUs
Cotellictablet20 mgoralHoffmann La Roche Limited2016-04-06Not applicableCanada
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Cobimetinib fumarate
1369665-02-0
Thumb
  • InChI Key: RESIMIUSNACMNW-BXRWSSRYSA-N
  • Monoisotopic Mass: 1178.13707
  • Average Mass: 1178.707
DBSALT001290
Categories
UNIIER29L26N1X
CAS number934660-93-2
WeightAverage: 531.318
Monoisotopic: 531.06306
Chemical FormulaC21H21F3IN3O2
InChI KeyBSMCAPRUBJMWDF-KRWDZBQOSA-N
InChI
InChI=1S/C21H21F3IN3O2/c22-14-6-5-13(19(18(14)24)27-16-7-4-12(25)9-15(16)23)20(29)28-10-21(30,11-28)17-3-1-2-8-26-17/h4-7,9,17,26-27,30H,1-3,8,10-11H2/t17-/m0/s1
IUPAC Name
1-{3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]benzoyl}-3-[(2S)-piperidin-2-yl]azetidin-3-ol
SMILES
OC1(CN(C1)C(=O)C1=C(NC2=C(F)C=C(I)C=C2)C(F)=C(F)C=C1)[C@@H]1CCCCN1
Taxonomy
ClassificationNot classified
Pharmacology
IndicationFor the treatment of patients with unresectable or metastatic melanoma with a BRAF V600E or V600K mutation. Cobimetinib is used in combination with vemurafenib, a BRAF inhibitor.
PharmacodynamicsCobimetinib is a reversible inhibitor of mitogen-activated protein kinase 1 (MAPK)/extracellular signal regulated kinase 1 (MEK1) and MEK2. Preclinical studies have demonstrated that this agent is effective in inhibiting the growth of tumor cells bearing a BRAF mutation, which has been found to be associated with many tumor types. A threonine-tyrosine kinase and a key component of the RAS/RAF/MEK/ERK signalling pathway that is frequently activated in human tumors, MEK1 is required for the transmission of growth-promoting signals from numerous receptor tyrosine kinases. Cobimetinib is used in combination with vemurafenib because the clinical benefit of a BRAF inhibitor is limited by intrinsic and acquired resistance. Reactivation of the MAPK pathway is a major contributor to treatment failure in BRAF-mutant melanomas, approximately ~80% of melanoma tumors becomes BRAF-inhibitor resistant due to reactivation of MAPK signalling. BRAF-inhibitor resistant tumor cells are sensitive to MEK inhibition, therefore cobimetinib and vemurafenib will result in dual inhibition of BRAF and its downstream target, MEK.
Mechanism of actionMEK inhibitor Cobimetinib specifically binds to and inhibits the catalytic activity of MEK1, resulting in inhibition of extracellular signal-related kinase 2 (ERK2) phosphorylation and activation and decreased tumor cell proliferation. Cobimetinib and vemurafenib target two different kinases in the RAS/RAF/MEK/ERK pathway.
Related Articles
AbsorptionThe bioavailability of cobimetinib is 46%, the AUC and Cmax is unaffected by food.
Volume of distribution

806L in cancer patients based on a population PK analysis.

Protein binding95% bound to human plasma protein.
Metabolism

Cobimetinib is mainly metabolized via CYP3A oxidation and UGT2B7 glucuronidation with no major metabolites formed.

Route of elimination76% of the dose was recovered in feces with 6.6% as unchanged drug. 17.8% of the dose was recovered in urine with 1.6% as unchanged drug.
Half lifeAverage half life was 44 hours.
Clearance

13.9L/h

ToxicityThe most common adverse effects (>20%) for cobimetinib are diarrhea, photosensitivity reactions, nausea, fever and vomiting.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal AbsorptionNot AvailableNot Available
Blood Brain BarrierNot AvailableNot Available
Caco-2 permeableNot AvailableNot Available
P-glycoprotein substrateNot AvailableNot Available
P-glycoprotein inhibitor INot AvailableNot Available
P-glycoprotein inhibitor IINot AvailableNot Available
Renal organic cation transporterNot AvailableNot Available
CYP450 2C9 substrateNot AvailableNot Available
CYP450 2D6 substrateNot AvailableNot Available
CYP450 3A4 substrateNot AvailableNot Available
CYP450 1A2 substrateNot AvailableNot Available
CYP450 2C9 inhibitorNot AvailableNot Available
CYP450 2D6 inhibitorNot AvailableNot Available
CYP450 2C19 inhibitorNot AvailableNot Available
CYP450 3A4 inhibitorNot AvailableNot Available
CYP450 inhibitory promiscuityNot AvailableNot Available
Ames testNot AvailableNot Available
CarcinogenicityNot AvailableNot Available
BiodegradationNot AvailableNot Available
Rat acute toxicityNot AvailableNot applicable
hERG inhibition (predictor I)Not AvailableNot Available
hERG inhibition (predictor II)Not AvailableNot Available
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
Tabletoral20 mg
Tablet, film coatedoral20 mg/1
PricesNot Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US7803839 No2007-02-012027-02-01Us
US8362002 No2006-10-052026-10-05Us
Properties
StateSolid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.0422 mg/mLALOGPS
logP3.35ALOGPS
logP5.04ChemAxon
logS-4.1ALOGPS
pKa (Strongest Acidic)13.37ChemAxon
pKa (Strongest Basic)9.76ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area64.6 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity115.85 m3·mol-1ChemAxon
Polarizability44.75 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis ReferenceNot Available
General References
  1. Garnock-Jones KP: Cobimetinib: First Global Approval. Drugs. 2015 Oct;75(15):1823-30. doi: 10.1007/s40265-015-0477-8. [PubMed:26452567 ]
  2. Han K, Jin JY, Marchand M, Eppler S, Choong N, Hack SP, Tikoo N, Bruno R, Dresser M, Musib L, Budha NR: Population pharmacokinetics and dosing implications for cobimetinib in patients with solid tumors. Cancer Chemother Pharmacol. 2015 Nov;76(5):917-24. doi: 10.1007/s00280-015-2862-0. Epub 2015 Sep 13. [PubMed:26365290 ]
  3. Singh A, Ruan Y, Tippett T, Narendran A: Targeted inhibition of MEK1 by cobimetinib leads to differentiation and apoptosis in neuroblastoma cells. J Exp Clin Cancer Res. 2015 Sep 18;34:104. doi: 10.1186/s13046-015-0222-x. [PubMed:26384788 ]
  4. Tran KA, Cheng MY, Mitra A, Ogawa H, Shi VY, Olney LP, Kloxin AM, Maverakis E: MEK inhibitors and their potential in the treatment of advanced melanoma: the advantages of combination therapy. Drug Des Devel Ther. 2015 Dec 21;10:43-52. doi: 10.2147/DDDT.S93545. eCollection 2016. [PubMed:26730180 ]
  5. Takahashi RH, Choo EF, Ma S, Wong S, Halladay J, Deng Y, Rooney I, Gates M, Hop CE, Khojasteh SC, Dresser MJ, Musib L: Absorption, Metabolism, Excretion, and the Contribution of Intestinal Metabolism to the Oral Disposition of [14C]Cobimetinib, a MEK Inhibitor, in Humans. Drug Metab Dispos. 2016 Jan;44(1):28-39. doi: 10.1124/dmd.115.066282. Epub 2015 Oct 8. [PubMed:26451002 ]
External Links
ATC CodesNot Available
AHFS Codes
  • 10:00
PDB EntriesNot Available
FDA labelDownload (324 KB)
MSDSNot Available
Interactions
Drug Interactions
Drug
AcetaminophenThe serum concentration of Cobimetinib can be increased when it is combined with Acetaminophen.
AfatinibThe serum concentration of Cobimetinib can be increased when it is combined with Afatinib.
AlbendazoleThe serum concentration of Cobimetinib can be increased when it is combined with Albendazole.
AldosteroneThe serum concentration of Cobimetinib can be decreased when it is combined with Aldosterone.
AlectinibThe serum concentration of Cobimetinib can be increased when it is combined with Alectinib.
AlfentanilThe serum concentration of Cobimetinib can be increased when it is combined with Alfentanil.
AmantadineThe serum concentration of Cobimetinib can be increased when it is combined with Amantadine.
Aminohippuric acidThe serum concentration of Cobimetinib can be increased when it is combined with Aminohippuric acid.
AmiodaroneThe serum concentration of Cobimetinib can be increased when it is combined with Amiodarone.
AmitriptylineThe serum concentration of Cobimetinib can be increased when it is combined with Amitriptyline.
AmlodipineThe serum concentration of Cobimetinib can be increased when it is combined with Amlodipine.
AmprenavirThe serum concentration of Cobimetinib can be decreased when it is combined with Amprenavir.
AmsacrineThe serum concentration of Cobimetinib can be increased when it is combined with Amsacrine.
AprepitantThe serum concentration of Cobimetinib can be increased when it is combined with Aprepitant.
AstemizoleThe serum concentration of Cobimetinib can be increased when it is combined with Astemizole.
AtazanavirThe serum concentration of Cobimetinib can be increased when it is combined with Atazanavir.
AtenololThe serum concentration of Cobimetinib can be increased when it is combined with Atenolol.
AtomoxetineThe serum concentration of Cobimetinib can be increased when it is combined with Atomoxetine.
AtorvastatinThe serum concentration of Cobimetinib can be increased when it is combined with Atorvastatin.
AzelastineThe serum concentration of Cobimetinib can be increased when it is combined with Azelastine.
AzithromycinThe serum concentration of Cobimetinib can be increased when it is combined with Azithromycin.
BenzocaineThe serum concentration of Cobimetinib can be increased when it is combined with Benzocaine.
BepridilThe serum concentration of Cobimetinib can be increased when it is combined with Bepridil.
BexaroteneThe serum concentration of Cobimetinib can be decreased when it is combined with Bexarotene.
BiperidenThe serum concentration of Cobimetinib can be increased when it is combined with Biperiden.
BoceprevirThe serum concentration of Cobimetinib can be increased when it is combined with Boceprevir.
BortezomibThe serum concentration of Cobimetinib can be increased when it is combined with Bortezomib.
BosentanThe serum concentration of Cobimetinib can be decreased when it is combined with Bosentan.
BosutinibThe serum concentration of Cobimetinib can be increased when it is combined with Bosutinib.
BromocriptineThe serum concentration of Cobimetinib can be increased when it is combined with Bromocriptine.
BuprenorphineThe serum concentration of Cobimetinib can be increased when it is combined with Buprenorphine.
BuspironeThe serum concentration of Cobimetinib can be increased when it is combined with Buspirone.
CabazitaxelThe serum concentration of Cobimetinib can be increased when it is combined with Cabazitaxel.
CaffeineThe serum concentration of Cobimetinib can be increased when it is combined with Caffeine.
CanagliflozinThe serum concentration of Cobimetinib can be increased when it is combined with Canagliflozin.
CandesartanThe serum concentration of Cobimetinib can be increased when it is combined with Candesartan.
CaptoprilThe serum concentration of Cobimetinib can be increased when it is combined with Captopril.
CarbamazepineThe serum concentration of Cobimetinib can be decreased when it is combined with Carbamazepine.
CarvedilolThe serum concentration of Cobimetinib can be increased when it is combined with Carvedilol.
CaspofunginThe serum concentration of Cobimetinib can be increased when it is combined with Caspofungin.
CeritinibThe serum concentration of Cobimetinib can be increased when it is combined with Ceritinib.
ChloroquineThe serum concentration of Cobimetinib can be increased when it is combined with Chloroquine.
ChlorpromazineThe serum concentration of Cobimetinib can be increased when it is combined with Chlorpromazine.
ChlorpropamideThe serum concentration of Cobimetinib can be increased when it is combined with Chlorpropamide.
ChlorprothixeneThe serum concentration of Cobimetinib can be increased when it is combined with Chlorprothixene.
CholesterolThe serum concentration of Cobimetinib can be increased when it is combined with Cholesterol.
Cholic AcidThe serum concentration of Cobimetinib can be decreased when it is combined with Cholic Acid.
CilazaprilThe serum concentration of Cobimetinib can be increased when it is combined with Cilazapril.
CimetidineThe serum concentration of Cobimetinib can be decreased when it is combined with Cimetidine.
CiprofloxacinThe serum concentration of Cobimetinib can be increased when it is combined with Ciprofloxacin.
CitalopramThe serum concentration of Cobimetinib can be increased when it is combined with Citalopram.
ClarithromycinThe serum concentration of Cobimetinib can be increased when it is combined with Clarithromycin.
ClemastineThe serum concentration of Cobimetinib can be increased when it is combined with Clemastine.
ClofazimineThe serum concentration of Cobimetinib can be increased when it is combined with Clofazimine.
ClomipramineThe serum concentration of Cobimetinib can be increased when it is combined with Clomipramine.
ClotrimazoleThe serum concentration of Cobimetinib can be increased when it is combined with Clotrimazole.
CobicistatThe serum concentration of Cobimetinib can be increased when it is combined with Cobicistat.
ColchicineThe serum concentration of Cobimetinib can be increased when it is combined with Colchicine.
ColforsinThe serum concentration of Cobimetinib can be increased when it is combined with Colforsin.
ConivaptanThe serum concentration of Cobimetinib can be increased when it is combined with Conivaptan.
CrizotinibThe serum concentration of Cobimetinib can be increased when it is combined with Crizotinib.
CyclophosphamideThe serum concentration of Cobimetinib can be increased when it is combined with Cyclophosphamide.
CyclosporineThe serum concentration of Cobimetinib can be increased when it is combined with Cyclosporine.
DabrafenibThe serum concentration of Cobimetinib can be decreased when it is combined with Dabrafenib.
DaclatasvirThe serum concentration of Cobimetinib can be increased when it is combined with Daclatasvir.
DactinomycinThe serum concentration of Cobimetinib can be increased when it is combined with Dactinomycin.
DarunavirThe serum concentration of Cobimetinib can be increased when it is combined with Darunavir.
DasatinibThe serum concentration of Cobimetinib can be increased when it is combined with Dasatinib.
DaunorubicinThe serum concentration of Cobimetinib can be decreased when it is combined with Daunorubicin.
DelavirdineThe serum concentration of Cobimetinib can be increased when it is combined with Delavirdine.
DesipramineThe serum concentration of Cobimetinib can be increased when it is combined with Desipramine.
DesloratadineThe serum concentration of Cobimetinib can be increased when it is combined with Desloratadine.
DexamethasoneThe serum concentration of Cobimetinib can be decreased when it is combined with Dexamethasone.
DextromethorphanThe serum concentration of Cobimetinib can be increased when it is combined with Dextromethorphan.
DiclofenacThe serum concentration of Cobimetinib can be increased when it is combined with Diclofenac.
DigoxinThe serum concentration of Cobimetinib can be decreased when it is combined with Digoxin.
DihydroergotamineThe serum concentration of Cobimetinib can be increased when it is combined with Dihydroergotamine.
DiltiazemThe serum concentration of Cobimetinib can be increased when it is combined with Diltiazem.
DipyridamoleThe serum concentration of Cobimetinib can be increased when it is combined with Dipyridamole.
DoxazosinThe serum concentration of Cobimetinib can be increased when it is combined with Doxazosin.
DoxepinThe serum concentration of Cobimetinib can be increased when it is combined with Doxepin.
DoxorubicinThe serum concentration of Cobimetinib can be decreased when it is combined with Doxorubicin.
DoxycyclineThe serum concentration of Cobimetinib can be increased when it is combined with Doxycycline.
DronabinolThe serum concentration of Cobimetinib can be increased when it is combined with Dronabinol.
DronedaroneThe serum concentration of Cobimetinib can be increased when it is combined with Dronedarone.
EfavirenzThe serum concentration of Cobimetinib can be decreased when it is combined with Efavirenz.
ElbasvirThe serum concentration of Cobimetinib can be increased when it is combined with Elbasvir.
EltrombopagThe serum concentration of Cobimetinib can be increased when it is combined with Eltrombopag.
EnalaprilThe serum concentration of Cobimetinib can be increased when it is combined with Enalapril.
EnzalutamideThe serum concentration of Cobimetinib can be decreased when it is combined with Enzalutamide.
ErgonovineThe serum concentration of Cobimetinib can be increased when it is combined with Ergonovine.
ErgotamineThe serum concentration of Cobimetinib can be increased when it is combined with Ergotamine.
ErythromycinThe serum concentration of Cobimetinib can be increased when it is combined with Erythromycin.
Eslicarbazepine acetateThe serum concentration of Cobimetinib can be decreased when it is combined with Eslicarbazepine acetate.
EstramustineThe serum concentration of Cobimetinib can be increased when it is combined with Estramustine.
EstriolThe serum concentration of Cobimetinib can be decreased when it is combined with Estriol.
EstroneThe serum concentration of Cobimetinib can be decreased when it is combined with Estrone.
EtoposideThe serum concentration of Cobimetinib can be increased when it is combined with Etoposide.
EtravirineThe serum concentration of Cobimetinib can be decreased when it is combined with Etravirine.
FelodipineThe serum concentration of Cobimetinib can be increased when it is combined with Felodipine.
FentanylThe serum concentration of Cobimetinib can be increased when it is combined with Fentanyl.
FexofenadineThe serum concentration of Cobimetinib can be increased when it is combined with Fexofenadine.
FidaxomicinThe serum concentration of Cobimetinib can be increased when it is combined with Fidaxomicin.
FluconazoleThe serum concentration of Cobimetinib can be increased when it is combined with Fluconazole.
FluoxetineThe serum concentration of Cobimetinib can be increased when it is combined with Fluoxetine.
FlupentixolThe serum concentration of Cobimetinib can be increased when it is combined with Flupentixol.
FluphenazineThe serum concentration of Cobimetinib can be increased when it is combined with Fluphenazine.
FlurazepamThe serum concentration of Cobimetinib can be increased when it is combined with Flurazepam.
FluvoxamineThe serum concentration of Cobimetinib can be increased when it is combined with Fluvoxamine.
FosamprenavirThe serum concentration of Cobimetinib can be increased when it is combined with Fosamprenavir.
FosphenytoinThe serum concentration of Cobimetinib can be decreased when it is combined with Fosphenytoin.
GefitinibThe serum concentration of Cobimetinib can be increased when it is combined with Gefitinib.
GenisteinThe serum concentration of Cobimetinib can be increased when it is combined with Genistein.
GlyburideThe serum concentration of Cobimetinib can be increased when it is combined with Glyburide.
GlycerolThe serum concentration of Cobimetinib can be increased when it is combined with Glycerol.
Gramicidin DThe serum concentration of Cobimetinib can be increased when it is combined with Gramicidin D.
GrepafloxacinThe serum concentration of Cobimetinib can be increased when it is combined with Grepafloxacin.
HaloperidolThe serum concentration of Cobimetinib can be increased when it is combined with Haloperidol.
HydrocortisoneThe serum concentration of Cobimetinib can be increased when it is combined with Hydrocortisone.
IdelalisibThe serum concentration of Cobimetinib can be increased when it is combined with Idelalisib.
ImatinibThe serum concentration of Cobimetinib can be increased when it is combined with Imatinib.
ImipramineThe serum concentration of Cobimetinib can be increased when it is combined with Imipramine.
IndinavirThe serum concentration of Cobimetinib can be increased when it is combined with Indinavir.
IndomethacinThe serum concentration of Cobimetinib can be increased when it is combined with Indomethacin.
IsavuconazoniumThe serum concentration of Cobimetinib can be increased when it is combined with Isavuconazonium.
IsradipineThe serum concentration of Cobimetinib can be increased when it is combined with Isradipine.
ItraconazoleThe serum concentration of Cobimetinib can be increased when it is combined with Itraconazole.
IvacaftorThe serum concentration of Cobimetinib can be increased when it is combined with Ivacaftor.
IvermectinThe serum concentration of Cobimetinib can be increased when it is combined with Ivermectin.
KetamineThe serum concentration of Cobimetinib can be increased when it is combined with Ketamine.
KetoconazoleThe serum concentration of Cobimetinib can be increased when it is combined with Ketoconazole.
LansoprazoleThe serum concentration of Cobimetinib can be increased when it is combined with Lansoprazole.
LapatinibThe serum concentration of Cobimetinib can be increased when it is combined with Lapatinib.
LevofloxacinThe serum concentration of Cobimetinib can be increased when it is combined with Levofloxacin.
LevothyroxineThe serum concentration of Cobimetinib can be decreased when it is combined with Levothyroxine.
LidocaineThe serum concentration of Cobimetinib can be increased when it is combined with Lidocaine.
LiothyronineThe serum concentration of Cobimetinib can be decreased when it is combined with Liothyronine.
LiotrixThe serum concentration of Cobimetinib can be decreased when it is combined with Liotrix.
LisinoprilThe serum concentration of Cobimetinib can be increased when it is combined with Lisinopril.
LomitapideThe serum concentration of Cobimetinib can be increased when it is combined with Lomitapide.
LoperamideThe serum concentration of Cobimetinib can be increased when it is combined with Loperamide.
LopinavirThe serum concentration of Cobimetinib can be increased when it is combined with Lopinavir.
LoratadineThe serum concentration of Cobimetinib can be increased when it is combined with Loratadine.
LosartanThe serum concentration of Cobimetinib can be increased when it is combined with Losartan.
LovastatinThe serum concentration of Cobimetinib can be increased when it is combined with Lovastatin.
LuliconazoleThe serum concentration of Cobimetinib can be increased when it is combined with Luliconazole.
LumacaftorThe serum concentration of Cobimetinib can be decreased when it is combined with Lumacaftor.
MaprotilineThe serum concentration of Cobimetinib can be increased when it is combined with Maprotiline.
MebendazoleThe serum concentration of Cobimetinib can be increased when it is combined with Mebendazole.
MefloquineThe serum concentration of Cobimetinib can be increased when it is combined with Mefloquine.
Megestrol acetateThe serum concentration of Cobimetinib can be increased when it is combined with Megestrol acetate.
MeprobamateThe serum concentration of Cobimetinib can be increased when it is combined with Meprobamate.
MethadoneThe serum concentration of Cobimetinib can be increased when it is combined with Methadone.
MetoprololThe serum concentration of Cobimetinib can be increased when it is combined with Metoprolol.
MibefradilThe serum concentration of Cobimetinib can be increased when it is combined with Mibefradil.
MiconazoleThe serum concentration of Cobimetinib can be increased when it is combined with Miconazole.
MidazolamThe serum concentration of Cobimetinib can be decreased when it is combined with Midazolam.
MifepristoneThe serum concentration of Cobimetinib can be increased when it is combined with Mifepristone.
MitomycinThe serum concentration of Cobimetinib can be increased when it is combined with Mitomycin.
MitotaneThe serum concentration of Cobimetinib can be decreased when it is combined with Mitotane.
MitoxantroneThe serum concentration of Cobimetinib can be decreased when it is combined with Mitoxantrone.
ModafinilThe serum concentration of Cobimetinib can be decreased when it is combined with Modafinil.
MorphineThe serum concentration of Cobimetinib can be increased when it is combined with Morphine.
NafcillinThe serum concentration of Cobimetinib can be decreased when it is combined with Nafcillin.
NaltrexoneThe serum concentration of Cobimetinib can be increased when it is combined with Naltrexone.
NaringeninThe serum concentration of Cobimetinib can be increased when it is combined with Naringenin.
NefazodoneThe serum concentration of Cobimetinib can be increased when it is combined with Nefazodone.
NelfinavirThe serum concentration of Cobimetinib can be increased when it is combined with Nelfinavir.
NeostigmineThe serum concentration of Cobimetinib can be increased when it is combined with Neostigmine.
NetupitantThe serum concentration of Cobimetinib can be increased when it is combined with Netupitant.
NevirapineThe serum concentration of Cobimetinib can be decreased when it is combined with Nevirapine.
NicardipineThe serum concentration of Cobimetinib can be increased when it is combined with Nicardipine.
NifedipineThe serum concentration of Cobimetinib can be decreased when it is combined with Nifedipine.
NilotinibThe serum concentration of Cobimetinib can be increased when it is combined with Nilotinib.
NisoldipineThe serum concentration of Cobimetinib can be increased when it is combined with Nisoldipine.
NitrazepamThe serum concentration of Cobimetinib can be increased when it is combined with Nitrazepam.
NitrendipineThe serum concentration of Cobimetinib can be increased when it is combined with Nitrendipine.
NorethisteroneThe serum concentration of Cobimetinib can be decreased when it is combined with Norethisterone.
OlaparibThe serum concentration of Cobimetinib can be increased when it is combined with Olaparib.
OmeprazoleThe serum concentration of Cobimetinib can be increased when it is combined with Omeprazole.
P-NitrophenolThe serum concentration of Cobimetinib can be increased when it is combined with P-Nitrophenol.
PaclitaxelThe serum concentration of Cobimetinib can be increased when it is combined with Paclitaxel.
Palmitic AcidThe serum concentration of Cobimetinib can be increased when it is combined with Palmitic Acid.
PantoprazoleThe serum concentration of Cobimetinib can be increased when it is combined with Pantoprazole.
ParoxetineThe serum concentration of Cobimetinib can be increased when it is combined with Paroxetine.
PentobarbitalThe serum concentration of Cobimetinib can be decreased when it is combined with Pentobarbital.
PerindoprilThe serum concentration of Cobimetinib can be increased when it is combined with Perindopril.
PhenobarbitalThe serum concentration of Cobimetinib can be decreased when it is combined with Phenobarbital.
PhenytoinThe serum concentration of Cobimetinib can be decreased when it is combined with Phenytoin.
PimozideThe serum concentration of Cobimetinib can be increased when it is combined with Pimozide.
Platelet Activating FactorThe serum concentration of Cobimetinib can be decreased when it is combined with Platelet Activating Factor.
PonatinibThe serum concentration of Cobimetinib can be increased when it is combined with Ponatinib.
PosaconazoleThe serum concentration of Cobimetinib can be increased when it is combined with Posaconazole.
PravastatinThe serum concentration of Cobimetinib can be increased when it is combined with Pravastatin.
PrazosinThe serum concentration of Cobimetinib can be increased when it is combined with Prazosin.
PrednisoneThe serum concentration of Cobimetinib can be increased when it is combined with Prednisone.
PrimidoneThe serum concentration of Cobimetinib can be decreased when it is combined with Primidone.
ProbenecidThe serum concentration of Cobimetinib can be increased when it is combined with Probenecid.
ProgesteroneThe serum concentration of Cobimetinib can be decreased when it is combined with Progesterone.
PromethazineThe serum concentration of Cobimetinib can be increased when it is combined with Promethazine.
PropafenoneThe serum concentration of Cobimetinib can be increased when it is combined with Propafenone.
PropranololThe serum concentration of Cobimetinib can be increased when it is combined with Propranolol.
ProtriptylineThe serum concentration of Cobimetinib can be increased when it is combined with Protriptyline.
QuercetinThe serum concentration of Cobimetinib can be increased when it is combined with Quercetin.
QuinacrineThe serum concentration of Cobimetinib can be increased when it is combined with Quinacrine.
QuinidineThe serum concentration of Cobimetinib can be increased when it is combined with Quinidine.
QuinineThe serum concentration of Cobimetinib can be increased when it is combined with Quinine.
RanitidineThe serum concentration of Cobimetinib can be increased when it is combined with Ranitidine.
RanolazineThe serum concentration of Cobimetinib can be increased when it is combined with Ranolazine.
ReboxetineThe serum concentration of Cobimetinib can be increased when it is combined with Reboxetine.
RegorafenibThe serum concentration of Cobimetinib can be increased when it is combined with Regorafenib.
ReserpineThe serum concentration of Cobimetinib can be decreased when it is combined with Reserpine.
RifabutinThe serum concentration of Cobimetinib can be decreased when it is combined with Rifabutin.
RifampicinThe serum concentration of Cobimetinib can be decreased when it is combined with Rifampicin.
RifapentineThe serum concentration of Cobimetinib can be decreased when it is combined with Rifapentine.
RilpivirineThe serum concentration of Cobimetinib can be increased when it is combined with Rilpivirine.
RitonavirThe serum concentration of Cobimetinib can be increased when it is combined with Ritonavir.
RolapitantThe serum concentration of Cobimetinib can be increased when it is combined with Rolapitant.
SaquinavirThe serum concentration of Cobimetinib can be increased when it is combined with Saquinavir.
ScopolamineThe serum concentration of Cobimetinib can be increased when it is combined with Scopolamine.
SelegilineThe serum concentration of Cobimetinib can be increased when it is combined with Selegiline.
SertralineThe serum concentration of Cobimetinib can be increased when it is combined with Sertraline.
SildenafilThe serum concentration of Cobimetinib can be increased when it is combined with Sildenafil.
SimeprevirThe serum concentration of Cobimetinib can be increased when it is combined with Simeprevir.
SimvastatinThe serum concentration of Cobimetinib can be increased when it is combined with Simvastatin.
SirolimusThe serum concentration of Cobimetinib can be decreased when it is combined with Sirolimus.
SorafenibThe serum concentration of Cobimetinib can be increased when it is combined with Sorafenib.
SpironolactoneThe serum concentration of Cobimetinib can be increased when it is combined with Spironolactone.
St. John's WortThe serum concentration of Cobimetinib can be decreased when it is combined with St. John's Wort.
StaurosporineThe serum concentration of Cobimetinib can be increased when it is combined with Staurosporine.
StreptozocinThe serum concentration of Cobimetinib can be decreased when it is combined with Streptozocin.
SulfinpyrazoneThe serum concentration of Cobimetinib can be increased when it is combined with Sulfinpyrazone.
SulfisoxazoleThe serum concentration of Cobimetinib can be increased when it is combined with Sulfisoxazole.
SumatriptanThe serum concentration of Cobimetinib can be increased when it is combined with Sumatriptan.
SunitinibThe serum concentration of Cobimetinib can be increased when it is combined with Sunitinib.
TacrineThe serum concentration of Cobimetinib can be increased when it is combined with Tacrine.
TacrolimusThe serum concentration of Cobimetinib can be decreased when it is combined with Tacrolimus.
TamoxifenThe serum concentration of Cobimetinib can be decreased when it is combined with Tamoxifen.
Taurocholic AcidThe serum concentration of Cobimetinib can be increased when it is combined with Taurocholic Acid.
TelaprevirThe serum concentration of Cobimetinib can be increased when it is combined with Telaprevir.
TelithromycinThe serum concentration of Cobimetinib can be increased when it is combined with Telithromycin.
TelmisartanThe serum concentration of Cobimetinib can be increased when it is combined with Telmisartan.
TemsirolimusThe serum concentration of Cobimetinib can be increased when it is combined with Temsirolimus.
TerazosinThe serum concentration of Cobimetinib can be increased when it is combined with Terazosin.
TerfenadineThe serum concentration of Cobimetinib can be increased when it is combined with Terfenadine.
TeriflunomideThe serum concentration of Cobimetinib can be increased when it is combined with Teriflunomide.
TesmilifeneThe serum concentration of Cobimetinib can be decreased when it is combined with Tesmilifene.
TestosteroneThe serum concentration of Cobimetinib can be increased when it is combined with Testosterone.
TicagrelorThe serum concentration of Cobimetinib can be increased when it is combined with Ticagrelor.
TiclopidineThe serum concentration of Cobimetinib can be increased when it is combined with Ticlopidine.
TolvaptanThe serum concentration of Cobimetinib can be increased when it is combined with Tolvaptan.
TrazodoneThe serum concentration of Cobimetinib can be decreased when it is combined with Trazodone.
TrifluoperazineThe serum concentration of Cobimetinib can be increased when it is combined with Trifluoperazine.
TriflupromazineThe serum concentration of Cobimetinib can be increased when it is combined with Triflupromazine.
TrimethoprimThe serum concentration of Cobimetinib can be decreased when it is combined with Trimethoprim.
TrimipramineThe serum concentration of Cobimetinib can be increased when it is combined with Trimipramine.
TroleandomycinThe serum concentration of Cobimetinib can be increased when it is combined with Troleandomycin.
VenlafaxineThe serum concentration of Cobimetinib can be increased when it is combined with Venlafaxine.
VerapamilThe serum concentration of Cobimetinib can be increased when it is combined with Verapamil.
VinblastineThe serum concentration of Cobimetinib can be decreased when it is combined with Vinblastine.
VincristineThe serum concentration of Cobimetinib can be decreased when it is combined with Vincristine.
VinorelbineThe serum concentration of Cobimetinib can be increased when it is combined with Vinorelbine.
VoriconazoleThe serum concentration of Cobimetinib can be increased when it is combined with Voriconazole.
ZimelidineThe serum concentration of Cobimetinib can be increased when it is combined with Zimelidine.
ZiprasidoneThe serum concentration of Cobimetinib can be increased when it is combined with Ziprasidone.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Receptor signaling protein tyrosine phosphatase activity
Specific Function:
Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Binding of extracellular ligands such as growth factors, cytokines and hormones to their cell-surface receptors activates RAS and this initiates RAF1 activation. RAF1 then further activates the dual-specificity protein kinases MAP2K1/MEK1 and MAP2K2/MEK2. Both MAP2K1/MEK1 and MAP2...
Gene Name:
MAP2K1
Uniprot ID:
Q02750
Molecular Weight:
43438.65 Da
References
  1. Singh A, Ruan Y, Tippett T, Narendran A: Targeted inhibition of MEK1 by cobimetinib leads to differentiation and apoptosis in neuroblastoma cells. J Exp Clin Cancer Res. 2015 Sep 18;34:104. doi: 10.1186/s13046-015-0222-x. [PubMed:26384788 ]

Enzymes

Kind
Protein group
Organism
Human
Pharmacological action
unknown
Actions
substrate
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 reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide (PubMed:11159812). Catalyzes 4-beta-hydroxylation of cholesterol. May catalyze 25-hydroxylation of cholesterol in vitro (PubMed:21576599).
Components:
NameUniProt IDDetails
Cytochrome P450 3A4P08684 Details
Cytochrome P450 3A43Q9HB55 Details
Cytochrome P450 3A5P20815 Details
Cytochrome P450 3A7P24462 Details
References
  1. Singh A, Ruan Y, Tippett T, Narendran A: Targeted inhibition of MEK1 by cobimetinib leads to differentiation and apoptosis in neuroblastoma cells. J Exp Clin Cancer Res. 2015 Sep 18;34:104. doi: 10.1186/s13046-015-0222-x. [PubMed:26384788 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
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
Molecular Weight:
141477.255 Da
References
  1. Choo EF, Ly J, Chan J, Shahidi-Latham SK, Messick K, Plise E, Quiason CM, Yang L: Role of P-glycoprotein on the brain penetration and brain pharmacodynamic activity of the MEK inhibitor cobimetinib. Mol Pharm. 2014 Nov 3;11(11):4199-207. doi: 10.1021/mp500435s. Epub 2014 Oct 3. [PubMed:25243894 ]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrateweak inhibitor
General Function:
Sodium-independent organic anion transmembrane transporter activity
Specific Function:
Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostaglandin E2, thromboxane B2, leukotriene C3, leukotriene E4, thyroxine and triiodothyronine. Involved in the clearance of bile acids and organic anions from the liver.
Gene Name:
SLCO1B1
Uniprot ID:
Q9Y6L6
Molecular Weight:
76447.99 Da
References
  1. Singh A, Ruan Y, Tippett T, Narendran A: Targeted inhibition of MEK1 by cobimetinib leads to differentiation and apoptosis in neuroblastoma cells. J Exp Clin Cancer Res. 2015 Sep 18;34:104. doi: 10.1186/s13046-015-0222-x. [PubMed:26384788 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrateweak inhibitor
General Function:
Sodium-independent organic anion transmembrane transporter activity
Specific Function:
Mediates the Na(+)-independent uptake of organic anions such as 17-beta-glucuronosyl estradiol, taurocholate, triiodothyronine (T3), leukotriene C4, dehydroepiandrosterone sulfate (DHEAS), methotrexate and sulfobromophthalein (BSP). Involved in the clearance of bile acids and organic anions from the liver.
Gene Name:
SLCO1B3
Uniprot ID:
Q9NPD5
Molecular Weight:
77402.175 Da
References
  1. Singh A, Ruan Y, Tippett T, Narendran A: Targeted inhibition of MEK1 by cobimetinib leads to differentiation and apoptosis in neuroblastoma cells. J Exp Clin Cancer Res. 2015 Sep 18;34:104. doi: 10.1186/s13046-015-0222-x. [PubMed:26384788 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
weak 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 from mitochondria to cytosol and from cytosol to extracellular space, and cellular export of hemin, and heme. Xenobiotic transporter that may play an important role in the exclusion of xenobiotics from t...
Gene Name:
ABCG2
Uniprot ID:
Q9UNQ0
Molecular Weight:
72313.47 Da
References
  1. Choo EF, Ly J, Chan J, Shahidi-Latham SK, Messick K, Plise E, Quiason CM, Yang L: Role of P-glycoprotein on the brain penetration and brain pharmacodynamic activity of the MEK inhibitor cobimetinib. Mol Pharm. 2014 Nov 3;11(11):4199-207. doi: 10.1021/mp500435s. Epub 2014 Oct 3. [PubMed:25243894 ]
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Drug created on October 21, 2007 16:24 / Updated on September 27, 2016 02:28