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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
CotellicTablet20 mgOralHoffmann La Roche Limited2016-04-06Not applicableCanada
CotellicTablet, film coated20 mg/1OralGenentech, Inc.2015-11-10Not applicableUs
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
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.
Structured Indications
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.
TargetKindPharmacological actionActionsOrganismUniProt ID
Dual specificity mitogen-activated protein kinase kinase 1Proteinyes
inhibitor
HumanQ02750 details
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
Interactions
Drug Interactions
DrugInteractionDrug group
AcetaminophenThe serum concentration of Cobimetinib can be increased when it is combined with Acetaminophen.Approved
AfatinibThe serum concentration of Cobimetinib can be increased when it is combined with Afatinib.Approved
AlbendazoleThe serum concentration of Cobimetinib can be increased when it is combined with Albendazole.Approved, Vet Approved
AldosteroneThe serum concentration of Cobimetinib can be decreased when it is combined with Aldosterone.Experimental
AlectinibThe serum concentration of Cobimetinib can be increased when it is combined with Alectinib.Approved
AlfentanilThe serum concentration of Cobimetinib can be increased when it is combined with Alfentanil.Approved, Illicit
AmantadineThe serum concentration of Cobimetinib can be increased when it is combined with Amantadine.Approved
Aminohippuric acidThe serum concentration of Cobimetinib can be increased when it is combined with Aminohippuric acid.Approved
AmiodaroneThe serum concentration of Cobimetinib can be increased when it is combined with Amiodarone.Approved, Investigational
AmitriptylineThe serum concentration of Cobimetinib can be increased when it is combined with Amitriptyline.Approved
AmlodipineThe serum concentration of Cobimetinib can be increased when it is combined with Amlodipine.Approved
AmprenavirThe serum concentration of Cobimetinib can be decreased when it is combined with Amprenavir.Approved
AmsacrineThe serum concentration of Cobimetinib can be increased when it is combined with Amsacrine.Approved
AprepitantThe serum concentration of Cobimetinib can be increased when it is combined with Aprepitant.Approved, Investigational
AstemizoleThe serum concentration of Cobimetinib can be increased when it is combined with Astemizole.Approved, Withdrawn
AtazanavirThe serum concentration of Cobimetinib can be increased when it is combined with Atazanavir.Approved, Investigational
AtenololThe serum concentration of Cobimetinib can be increased when it is combined with Atenolol.Approved
AtomoxetineThe serum concentration of Cobimetinib can be increased when it is combined with Atomoxetine.Approved
AtorvastatinThe serum concentration of Cobimetinib can be increased when it is combined with Atorvastatin.Approved
AzelastineThe serum concentration of Cobimetinib can be increased when it is combined with Azelastine.Approved
AzithromycinThe serum concentration of Cobimetinib can be increased when it is combined with Azithromycin.Approved
BenzocaineThe serum concentration of Cobimetinib can be increased when it is combined with Benzocaine.Approved
BepridilThe serum concentration of Cobimetinib can be increased when it is combined with Bepridil.Approved, Withdrawn
BexaroteneThe serum concentration of Cobimetinib can be decreased when it is combined with Bexarotene.Approved, Investigational
BiperidenThe serum concentration of Cobimetinib can be increased when it is combined with Biperiden.Approved
BoceprevirThe serum concentration of Cobimetinib can be increased when it is combined with Boceprevir.Approved
BortezomibThe serum concentration of Cobimetinib can be increased when it is combined with Bortezomib.Approved, Investigational
BosentanThe serum concentration of Cobimetinib can be decreased when it is combined with Bosentan.Approved, Investigational
BosutinibThe serum concentration of Cobimetinib can be increased when it is combined with Bosutinib.Approved
BromocriptineThe serum concentration of Cobimetinib can be increased when it is combined with Bromocriptine.Approved, Investigational
BuprenorphineThe serum concentration of Cobimetinib can be increased when it is combined with Buprenorphine.Approved, Illicit, Investigational, Vet Approved
BuspironeThe serum concentration of Cobimetinib can be increased when it is combined with Buspirone.Approved, Investigational
CabazitaxelThe serum concentration of Cobimetinib can be increased when it is combined with Cabazitaxel.Approved
CaffeineThe serum concentration of Cobimetinib can be increased when it is combined with Caffeine.Approved
CanagliflozinThe serum concentration of Cobimetinib can be increased when it is combined with Canagliflozin.Approved
CandesartanThe serum concentration of Cobimetinib can be increased when it is combined with Candesartan.Approved
CaptoprilThe serum concentration of Cobimetinib can be increased when it is combined with Captopril.Approved
CarbamazepineThe serum concentration of Cobimetinib can be decreased when it is combined with Carbamazepine.Approved, Investigational
CarvedilolThe serum concentration of Cobimetinib can be increased when it is combined with Carvedilol.Approved, Investigational
CaspofunginThe serum concentration of Cobimetinib can be increased when it is combined with Caspofungin.Approved
CeritinibThe serum concentration of Cobimetinib can be increased when it is combined with Ceritinib.Approved
ChloroquineThe serum concentration of Cobimetinib can be increased when it is combined with Chloroquine.Approved, Vet Approved
ChlorpromazineThe serum concentration of Cobimetinib can be increased when it is combined with Chlorpromazine.Approved, Vet Approved
ChlorpropamideThe serum concentration of Cobimetinib can be increased when it is combined with Chlorpropamide.Approved
ChlorprothixeneThe serum concentration of Cobimetinib can be increased when it is combined with Chlorprothixene.Approved, Withdrawn
CholesterolThe serum concentration of Cobimetinib can be increased when it is combined with Cholesterol.Experimental
Cholic AcidThe serum concentration of Cobimetinib can be decreased when it is combined with Cholic Acid.Approved
CilazaprilThe serum concentration of Cobimetinib can be increased when it is combined with Cilazapril.Approved
CimetidineThe serum concentration of Cobimetinib can be decreased when it is combined with Cimetidine.Approved
CiprofloxacinThe serum concentration of Cobimetinib can be increased when it is combined with Ciprofloxacin.Approved, Investigational
CitalopramThe serum concentration of Cobimetinib can be increased when it is combined with Citalopram.Approved
ClarithromycinThe serum concentration of Cobimetinib can be increased when it is combined with Clarithromycin.Approved
ClemastineThe serum concentration of Cobimetinib can be increased when it is combined with Clemastine.Approved
ClofazimineThe serum concentration of Cobimetinib can be increased when it is combined with Clofazimine.Approved, Investigational
ClomipramineThe serum concentration of Cobimetinib can be increased when it is combined with Clomipramine.Approved, Vet Approved
ClotrimazoleThe serum concentration of Cobimetinib can be increased when it is combined with Clotrimazole.Approved, Vet Approved
CobicistatThe serum concentration of Cobimetinib can be increased when it is combined with Cobicistat.Approved
ColchicineThe serum concentration of Cobimetinib can be increased when it is combined with Colchicine.Approved
ColforsinThe serum concentration of Cobimetinib can be increased when it is combined with Colforsin.Experimental
ConivaptanThe serum concentration of Cobimetinib can be increased when it is combined with Conivaptan.Approved, Investigational
CrizotinibThe serum concentration of Cobimetinib can be increased when it is combined with Crizotinib.Approved
CyclophosphamideThe serum concentration of Cobimetinib can be increased when it is combined with Cyclophosphamide.Approved, Investigational
CyclosporineThe serum concentration of Cobimetinib can be increased when it is combined with Cyclosporine.Approved, Investigational, Vet Approved
DabrafenibThe serum concentration of Cobimetinib can be decreased when it is combined with Dabrafenib.Approved
DaclatasvirThe serum concentration of Cobimetinib can be increased when it is combined with Daclatasvir.Approved
DactinomycinThe serum concentration of Cobimetinib can be increased when it is combined with Dactinomycin.Approved
DarunavirThe serum concentration of Cobimetinib can be increased when it is combined with Darunavir.Approved
DasatinibThe serum concentration of Cobimetinib can be increased when it is combined with Dasatinib.Approved, Investigational
DaunorubicinThe serum concentration of Cobimetinib can be decreased when it is combined with Daunorubicin.Approved
DelavirdineThe serum concentration of Cobimetinib can be increased when it is combined with Delavirdine.Approved
DesipramineThe serum concentration of Cobimetinib can be increased when it is combined with Desipramine.Approved
DesloratadineThe serum concentration of Cobimetinib can be increased when it is combined with Desloratadine.Approved, Investigational
DexamethasoneThe serum concentration of Cobimetinib can be decreased when it is combined with Dexamethasone.Approved, Investigational, Vet Approved
DextromethorphanThe serum concentration of Cobimetinib can be increased when it is combined with Dextromethorphan.Approved
DiclofenacThe serum concentration of Cobimetinib can be increased when it is combined with Diclofenac.Approved, Vet Approved
DigoxinThe serum concentration of Cobimetinib can be decreased when it is combined with Digoxin.Approved
DihydroergotamineThe serum concentration of Cobimetinib can be increased when it is combined with Dihydroergotamine.Approved
DiltiazemThe serum concentration of Cobimetinib can be increased when it is combined with Diltiazem.Approved
DipyridamoleThe serum concentration of Cobimetinib can be increased when it is combined with Dipyridamole.Approved
DoxazosinThe serum concentration of Cobimetinib can be increased when it is combined with Doxazosin.Approved
DoxepinThe serum concentration of Cobimetinib can be increased when it is combined with Doxepin.Approved
DoxorubicinThe serum concentration of Cobimetinib can be decreased when it is combined with Doxorubicin.Approved, Investigational
DoxycyclineThe serum concentration of Cobimetinib can be increased when it is combined with Doxycycline.Approved, Investigational, Vet Approved
DronabinolThe serum concentration of Cobimetinib can be increased when it is combined with Dronabinol.Approved, Illicit
DronedaroneThe serum concentration of Cobimetinib can be increased when it is combined with Dronedarone.Approved
EfavirenzThe serum concentration of Cobimetinib can be decreased when it is combined with Efavirenz.Approved, Investigational
ElbasvirThe serum concentration of Cobimetinib can be increased when it is combined with Elbasvir.Approved
EltrombopagThe serum concentration of Cobimetinib can be increased when it is combined with Eltrombopag.Approved
EnalaprilThe serum concentration of Cobimetinib can be increased when it is combined with Enalapril.Approved, Vet Approved
EnzalutamideThe serum concentration of Cobimetinib can be decreased when it is combined with Enzalutamide.Approved
ErgonovineThe serum concentration of Cobimetinib can be increased when it is combined with Ergonovine.Approved
ErgotamineThe serum concentration of Cobimetinib can be increased when it is combined with Ergotamine.Approved
ErythromycinThe serum concentration of Cobimetinib can be increased when it is combined with Erythromycin.Approved, Vet Approved
Eslicarbazepine acetateThe serum concentration of Cobimetinib can be decreased when it is combined with Eslicarbazepine acetate.Approved
EstramustineThe serum concentration of Cobimetinib can be increased when it is combined with Estramustine.Approved
EstriolThe serum concentration of Cobimetinib can be decreased when it is combined with Estriol.Approved, Vet Approved
EstroneThe serum concentration of Cobimetinib can be decreased when it is combined with Estrone.Approved
EtoposideThe serum concentration of Cobimetinib can be increased when it is combined with Etoposide.Approved
EtravirineThe serum concentration of Cobimetinib can be decreased when it is combined with Etravirine.Approved
FelodipineThe serum concentration of Cobimetinib can be increased when it is combined with Felodipine.Approved, Investigational
FentanylThe serum concentration of Cobimetinib can be increased when it is combined with Fentanyl.Approved, Illicit, Investigational, Vet Approved
FexofenadineThe serum concentration of Cobimetinib can be increased when it is combined with Fexofenadine.Approved
FidaxomicinThe serum concentration of Cobimetinib can be increased when it is combined with Fidaxomicin.Approved
FluconazoleThe serum concentration of Cobimetinib can be increased when it is combined with Fluconazole.Approved
FluoxetineThe serum concentration of Cobimetinib can be increased when it is combined with Fluoxetine.Approved, Vet Approved
FlupentixolThe serum concentration of Cobimetinib can be increased when it is combined with Flupentixol.Approved, Withdrawn
FluphenazineThe serum concentration of Cobimetinib can be increased when it is combined with Fluphenazine.Approved
FlurazepamThe serum concentration of Cobimetinib can be increased when it is combined with Flurazepam.Approved, Illicit
FluvoxamineThe serum concentration of Cobimetinib can be increased when it is combined with Fluvoxamine.Approved, Investigational
FosamprenavirThe serum concentration of Cobimetinib can be increased when it is combined with Fosamprenavir.Approved
FosphenytoinThe serum concentration of Cobimetinib can be decreased when it is combined with Fosphenytoin.Approved
GefitinibThe serum concentration of Cobimetinib can be increased when it is combined with Gefitinib.Approved, Investigational
GenisteinThe serum concentration of Cobimetinib can be increased when it is combined with Genistein.Investigational
GlyburideThe serum concentration of Cobimetinib can be increased when it is combined with Glyburide.Approved
GlycerolThe serum concentration of Cobimetinib can be increased when it is combined with Glycerol.Experimental
Gramicidin DThe serum concentration of Cobimetinib can be increased when it is combined with Gramicidin D.Approved
GrepafloxacinThe serum concentration of Cobimetinib can be increased when it is combined with Grepafloxacin.Withdrawn
HaloperidolThe serum concentration of Cobimetinib can be increased when it is combined with Haloperidol.Approved
HydrocortisoneThe serum concentration of Cobimetinib can be increased when it is combined with Hydrocortisone.Approved, Vet Approved
IdelalisibThe serum concentration of Cobimetinib can be increased when it is combined with Idelalisib.Approved
ImatinibThe serum concentration of Cobimetinib can be increased when it is combined with Imatinib.Approved
ImipramineThe serum concentration of Cobimetinib can be increased when it is combined with Imipramine.Approved
IndinavirThe serum concentration of Cobimetinib can be increased when it is combined with Indinavir.Approved
IndomethacinThe serum concentration of Cobimetinib can be increased when it is combined with Indomethacin.Approved, Investigational
IsavuconazoniumThe serum concentration of Cobimetinib can be increased when it is combined with Isavuconazonium.Approved, Investigational
IsradipineThe serum concentration of Cobimetinib can be increased when it is combined with Isradipine.Approved
ItraconazoleThe serum concentration of Cobimetinib can be increased when it is combined with Itraconazole.Approved, Investigational
IvacaftorThe serum concentration of Cobimetinib can be increased when it is combined with Ivacaftor.Approved
IvermectinThe serum concentration of Cobimetinib can be increased when it is combined with Ivermectin.Approved, Vet Approved
KetamineThe serum concentration of Cobimetinib can be increased when it is combined with Ketamine.Approved, Vet Approved
KetoconazoleThe serum concentration of Cobimetinib can be increased when it is combined with Ketoconazole.Approved, Investigational
LansoprazoleThe serum concentration of Cobimetinib can be increased when it is combined with Lansoprazole.Approved, Investigational
LapatinibThe serum concentration of Cobimetinib can be increased when it is combined with Lapatinib.Approved, Investigational
LevofloxacinThe serum concentration of Cobimetinib can be increased when it is combined with Levofloxacin.Approved, Investigational
LevothyroxineThe serum concentration of Cobimetinib can be decreased when it is combined with Levothyroxine.Approved
LidocaineThe serum concentration of Cobimetinib can be increased when it is combined with Lidocaine.Approved, Vet Approved
LiothyronineThe serum concentration of Cobimetinib can be decreased when it is combined with Liothyronine.Approved, Vet Approved
LiotrixThe serum concentration of Cobimetinib can be decreased when it is combined with Liotrix.Approved
LisinoprilThe serum concentration of Cobimetinib can be increased when it is combined with Lisinopril.Approved, Investigational
LomitapideThe serum concentration of Cobimetinib can be increased when it is combined with Lomitapide.Approved
LoperamideThe serum concentration of Cobimetinib can be increased when it is combined with Loperamide.Approved
LopinavirThe serum concentration of Cobimetinib can be increased when it is combined with Lopinavir.Approved
LoratadineThe serum concentration of Cobimetinib can be increased when it is combined with Loratadine.Approved
LosartanThe serum concentration of Cobimetinib can be increased when it is combined with Losartan.Approved
LovastatinThe serum concentration of Cobimetinib can be increased when it is combined with Lovastatin.Approved, Investigational
LuliconazoleThe serum concentration of Cobimetinib can be increased when it is combined with Luliconazole.Approved
LumacaftorThe serum concentration of Cobimetinib can be decreased when it is combined with Lumacaftor.Approved
MaprotilineThe serum concentration of Cobimetinib can be increased when it is combined with Maprotiline.Approved
MebendazoleThe serum concentration of Cobimetinib can be increased when it is combined with Mebendazole.Approved, Vet Approved
MefloquineThe serum concentration of Cobimetinib can be increased when it is combined with Mefloquine.Approved
Megestrol acetateThe serum concentration of Cobimetinib can be increased when it is combined with Megestrol acetate.Approved, Vet Approved
MeprobamateThe serum concentration of Cobimetinib can be increased when it is combined with Meprobamate.Approved, Illicit
MethadoneThe serum concentration of Cobimetinib can be increased when it is combined with Methadone.Approved
MetoprololThe serum concentration of Cobimetinib can be increased when it is combined with Metoprolol.Approved, Investigational
MibefradilThe serum concentration of Cobimetinib can be increased when it is combined with Mibefradil.Withdrawn
MiconazoleThe serum concentration of Cobimetinib can be increased when it is combined with Miconazole.Approved, Investigational, Vet Approved
MidazolamThe serum concentration of Cobimetinib can be decreased when it is combined with Midazolam.Approved, Illicit
MifepristoneThe serum concentration of Cobimetinib can be increased when it is combined with Mifepristone.Approved, Investigational
MitomycinThe serum concentration of Cobimetinib can be increased when it is combined with Mitomycin.Approved
MitotaneThe serum concentration of Cobimetinib can be decreased when it is combined with Mitotane.Approved
MitoxantroneThe serum concentration of Cobimetinib can be decreased when it is combined with Mitoxantrone.Approved, Investigational
ModafinilThe serum concentration of Cobimetinib can be decreased when it is combined with Modafinil.Approved, Investigational
MorphineThe serum concentration of Cobimetinib can be increased when it is combined with Morphine.Approved, Investigational
NafcillinThe serum concentration of Cobimetinib can be decreased when it is combined with Nafcillin.Approved
NaltrexoneThe serum concentration of Cobimetinib can be increased when it is combined with Naltrexone.Approved, Investigational, Vet Approved
NaringeninThe serum concentration of Cobimetinib can be increased when it is combined with Naringenin.Experimental
NefazodoneThe serum concentration of Cobimetinib can be increased when it is combined with Nefazodone.Approved, Withdrawn
NelfinavirThe serum concentration of Cobimetinib can be increased when it is combined with Nelfinavir.Approved
NeostigmineThe serum concentration of Cobimetinib can be increased when it is combined with Neostigmine.Approved, Vet Approved
NetupitantThe serum concentration of Cobimetinib can be increased when it is combined with Netupitant.Approved
NevirapineThe serum concentration of Cobimetinib can be decreased when it is combined with Nevirapine.Approved
NicardipineThe serum concentration of Cobimetinib can be increased when it is combined with Nicardipine.Approved
NifedipineThe serum concentration of Cobimetinib can be decreased when it is combined with Nifedipine.Approved
NilotinibThe serum concentration of Cobimetinib can be increased when it is combined with Nilotinib.Approved, Investigational
NisoldipineThe serum concentration of Cobimetinib can be increased when it is combined with Nisoldipine.Approved
NitrazepamThe serum concentration of Cobimetinib can be increased when it is combined with Nitrazepam.Approved
NitrendipineThe serum concentration of Cobimetinib can be increased when it is combined with Nitrendipine.Approved
NorethisteroneThe serum concentration of Cobimetinib can be decreased when it is combined with Norethisterone.Approved
OlaparibThe serum concentration of Cobimetinib can be increased when it is combined with Olaparib.Approved
OmeprazoleThe serum concentration of Cobimetinib can be increased when it is combined with Omeprazole.Approved, Investigational, Vet Approved
P-NitrophenolThe serum concentration of Cobimetinib can be increased when it is combined with P-Nitrophenol.Experimental
PaclitaxelThe serum concentration of Cobimetinib can be increased when it is combined with Paclitaxel.Approved, Vet Approved
Palmitic AcidThe serum concentration of Cobimetinib can be increased when it is combined with Palmitic Acid.Experimental
PantoprazoleThe serum concentration of Cobimetinib can be increased when it is combined with Pantoprazole.Approved
ParoxetineThe serum concentration of Cobimetinib can be increased when it is combined with Paroxetine.Approved, Investigational
PentobarbitalThe serum concentration of Cobimetinib can be decreased when it is combined with Pentobarbital.Approved, Vet Approved
PerindoprilThe serum concentration of Cobimetinib can be increased when it is combined with Perindopril.Approved
PhenobarbitalThe serum concentration of Cobimetinib can be decreased when it is combined with Phenobarbital.Approved
PhenytoinThe serum concentration of Cobimetinib can be decreased when it is combined with Phenytoin.Approved, Vet Approved
PimozideThe serum concentration of Cobimetinib can be increased when it is combined with Pimozide.Approved
Platelet Activating FactorThe serum concentration of Cobimetinib can be decreased when it is combined with Platelet Activating Factor.Experimental
PonatinibThe serum concentration of Cobimetinib can be increased when it is combined with Ponatinib.Approved
PosaconazoleThe serum concentration of Cobimetinib can be increased when it is combined with Posaconazole.Approved, Investigational, Vet Approved
PravastatinThe serum concentration of Cobimetinib can be increased when it is combined with Pravastatin.Approved
PrazosinThe serum concentration of Cobimetinib can be increased when it is combined with Prazosin.Approved
PrednisoneThe serum concentration of Cobimetinib can be increased when it is combined with Prednisone.Approved, Vet Approved
PrimidoneThe serum concentration of Cobimetinib can be decreased when it is combined with Primidone.Approved, Vet Approved
ProbenecidThe serum concentration of Cobimetinib can be increased when it is combined with Probenecid.Approved
ProgesteroneThe serum concentration of Cobimetinib can be decreased when it is combined with Progesterone.Approved, Vet Approved
PromethazineThe serum concentration of Cobimetinib can be increased when it is combined with Promethazine.Approved
PropafenoneThe serum concentration of Cobimetinib can be increased when it is combined with Propafenone.Approved
PropranololThe serum concentration of Cobimetinib can be increased when it is combined with Propranolol.Approved, Investigational
ProtriptylineThe serum concentration of Cobimetinib can be increased when it is combined with Protriptyline.Approved
QuercetinThe serum concentration of Cobimetinib can be increased when it is combined with Quercetin.Experimental
QuinacrineThe serum concentration of Cobimetinib can be increased when it is combined with Quinacrine.Approved
QuinidineThe serum concentration of Cobimetinib can be increased when it is combined with Quinidine.Approved
QuinineThe serum concentration of Cobimetinib can be increased when it is combined with Quinine.Approved
RanitidineThe serum concentration of Cobimetinib can be increased when it is combined with Ranitidine.Approved
RanolazineThe serum concentration of Cobimetinib can be increased when it is combined with Ranolazine.Approved, Investigational
ReboxetineThe serum concentration of Cobimetinib can be increased when it is combined with Reboxetine.Approved, Investigational
RegorafenibThe serum concentration of Cobimetinib can be increased when it is combined with Regorafenib.Approved
ReserpineThe serum concentration of Cobimetinib can be decreased when it is combined with Reserpine.Approved
RifabutinThe serum concentration of Cobimetinib can be decreased when it is combined with Rifabutin.Approved
RifampicinThe serum concentration of Cobimetinib can be decreased when it is combined with Rifampicin.Approved
RifapentineThe serum concentration of Cobimetinib can be decreased when it is combined with Rifapentine.Approved
RilpivirineThe serum concentration of Cobimetinib can be increased when it is combined with Rilpivirine.Approved
RitonavirThe serum concentration of Cobimetinib can be increased when it is combined with Ritonavir.Approved, Investigational
RolapitantThe serum concentration of Cobimetinib can be increased when it is combined with Rolapitant.Approved
SaquinavirThe serum concentration of Cobimetinib can be increased when it is combined with Saquinavir.Approved, Investigational
ScopolamineThe serum concentration of Cobimetinib can be increased when it is combined with Scopolamine.Approved
SelegilineThe serum concentration of Cobimetinib can be increased when it is combined with Selegiline.Approved, Investigational, Vet Approved
SertralineThe serum concentration of Cobimetinib can be increased when it is combined with Sertraline.Approved
SildenafilThe serum concentration of Cobimetinib can be increased when it is combined with Sildenafil.Approved, Investigational
SimeprevirThe serum concentration of Cobimetinib can be increased when it is combined with Simeprevir.Approved
SimvastatinThe serum concentration of Cobimetinib can be increased when it is combined with Simvastatin.Approved
SirolimusThe serum concentration of Cobimetinib can be decreased when it is combined with Sirolimus.Approved, Investigational
SorafenibThe serum concentration of Cobimetinib can be increased when it is combined with Sorafenib.Approved, Investigational
SpironolactoneThe serum concentration of Cobimetinib can be increased when it is combined with Spironolactone.Approved
St. John's WortThe serum concentration of Cobimetinib can be decreased when it is combined with St. John's Wort.Nutraceutical
StaurosporineThe serum concentration of Cobimetinib can be increased when it is combined with Staurosporine.Experimental
StreptozocinThe serum concentration of Cobimetinib can be decreased when it is combined with Streptozocin.Approved
SulfinpyrazoneThe serum concentration of Cobimetinib can be increased when it is combined with Sulfinpyrazone.Approved
SulfisoxazoleThe serum concentration of Cobimetinib can be increased when it is combined with Sulfisoxazole.Approved, Vet Approved
SumatriptanThe serum concentration of Cobimetinib can be increased when it is combined with Sumatriptan.Approved, Investigational
SunitinibThe serum concentration of Cobimetinib can be increased when it is combined with Sunitinib.Approved, Investigational
TacrineThe serum concentration of Cobimetinib can be increased when it is combined with Tacrine.Withdrawn
TacrolimusThe serum concentration of Cobimetinib can be decreased when it is combined with Tacrolimus.Approved, Investigational
TamoxifenThe serum concentration of Cobimetinib can be decreased when it is combined with Tamoxifen.Approved
Taurocholic AcidThe serum concentration of Cobimetinib can be increased when it is combined with Taurocholic Acid.Experimental
TelaprevirThe serum concentration of Cobimetinib can be increased when it is combined with Telaprevir.Approved
TelithromycinThe serum concentration of Cobimetinib can be increased when it is combined with Telithromycin.Approved
TelmisartanThe serum concentration of Cobimetinib can be increased when it is combined with Telmisartan.Approved, Investigational
TemsirolimusThe serum concentration of Cobimetinib can be increased when it is combined with Temsirolimus.Approved
TerazosinThe serum concentration of Cobimetinib can be increased when it is combined with Terazosin.Approved
TerfenadineThe serum concentration of Cobimetinib can be increased when it is combined with Terfenadine.Withdrawn
TeriflunomideThe serum concentration of Cobimetinib can be increased when it is combined with Teriflunomide.Approved
TesmilifeneThe serum concentration of Cobimetinib can be decreased when it is combined with Tesmilifene.Investigational
TestosteroneThe serum concentration of Cobimetinib can be increased when it is combined with Testosterone.Approved, Investigational
TicagrelorThe serum concentration of Cobimetinib can be increased when it is combined with Ticagrelor.Approved
TiclopidineThe serum concentration of Cobimetinib can be increased when it is combined with Ticlopidine.Approved
TolvaptanThe serum concentration of Cobimetinib can be increased when it is combined with Tolvaptan.Approved
TrazodoneThe serum concentration of Cobimetinib can be decreased when it is combined with Trazodone.Approved, Investigational
TrifluoperazineThe serum concentration of Cobimetinib can be increased when it is combined with Trifluoperazine.Approved
TriflupromazineThe serum concentration of Cobimetinib can be increased when it is combined with Triflupromazine.Approved, Vet Approved
TrimethoprimThe serum concentration of Cobimetinib can be decreased when it is combined with Trimethoprim.Approved, Vet Approved
TrimipramineThe serum concentration of Cobimetinib can be increased when it is combined with Trimipramine.Approved
TroleandomycinThe serum concentration of Cobimetinib can be increased when it is combined with Troleandomycin.Approved
VenlafaxineThe serum concentration of Cobimetinib can be increased when it is combined with Venlafaxine.Approved
VerapamilThe serum concentration of Cobimetinib can be increased when it is combined with Verapamil.Approved
VinblastineThe serum concentration of Cobimetinib can be decreased when it is combined with Vinblastine.Approved
VincristineThe serum concentration of Cobimetinib can be decreased when it is combined with Vincristine.Approved, Investigational
VinorelbineThe serum concentration of Cobimetinib can be increased when it is combined with Vinorelbine.Approved, Investigational
VoriconazoleThe serum concentration of Cobimetinib can be increased when it is combined with Voriconazole.Approved, Investigational
ZimelidineThe serum concentration of Cobimetinib can be increased when it is combined with Zimelidine.Withdrawn
ZiprasidoneThe serum concentration of Cobimetinib can be increased when it is combined with Ziprasidone.Approved
Food InteractionsNot 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
ADMET
Predicted ADMET featuresNot Available
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
Taxonomy
ClassificationNot classified

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 December 04, 2016 02:46