cobimetinib Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definitionDrug idCAS RN
MEK (MAPK kinase) tyrosine kinase inhibitors 5046 934660-93-2

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • cobimetinib
  • RG 7420
  • GDC-0973
  • cobimetinib butyrate
  • cobimetinib fumarate
  • cotellic
  • XL518
  • cobimetinib hemifumarate
Cobimetinib is a reversible inhibitor of mitogen-activated protein kinase (MAPK)/extracellular signal regulated kinase 1 (MEK1) and MEK2. MEK proteins are upstream regulators of the extracellular signal-related kinase (ERK) pathway, which promotes cellular proliferation. BRAF V600E and K mutations result in constitutive activation of the BRAF pathway which includes MEK1 and MEK2. In mice implanted with tumor cell lines expressing BRAF V600E, cobimetinib inhibited tumor cell growth.
  • Molecular weight: 531.32
  • Formula: C21H21F3IN3O2
  • CLOGP: 5.11
  • LIPINSKI: 2
  • HAC: 5
  • HDO: 3
  • TPSA: 64.60
  • ALOGS: -4.10
  • ROTB: 4

  • Status: ONP

  • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

None

ADMET properties:

PropertyValueReference
Vd (Volume of distribution) 15.40 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 2.80 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.05 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 68.80 hours Lombardo F, Berellini G, Obach RS

Approvals:

DateAgencyCompanyOrphan
Nov. 20, 2015 EMA
Nov. 10, 2015 FDA GENENTECH INC

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Drug reaction with eosinophilia and systemic symptoms 141.66 50.13 32 422 5486 2352145
Rash 137.77 50.13 53 401 59505 2298126
Pyrexia 124.70 50.13 48 406 53660 2303971
Diarrhoea 91.66 50.13 44 410 83520 2274111
Rash maculo-papular 78.90 50.13 19 435 4233 2353398
Toxic skin eruption 62.61 50.13 14 440 2246 2355385
Photosensitivity reaction 61.62 50.13 14 440 2413 2355218
Erythema multiforme 57.66 50.13 13 441 2162 2355469

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Rash 152.45 52.81 62 507 38631 1707581
Diarrhoea 117.18 52.81 57 512 53795 1692417
Photosensitivity reaction 109.05 52.81 24 545 1726 1744486
Pyrexia 106.42 52.81 51 518 46349 1699863
Uveitis 97.34 52.81 20 549 1031 1745181
Drug reaction with eosinophilia and systemic symptoms 88.22 52.81 25 544 5045 1741167
Acute kidney injury 69.47 52.81 35 534 34909 1711303
Rash maculo-papular 67.69 52.81 19 550 3684 1742528

Pharmacologic Action:

SourceCodeDescription
ATC L01XE38 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
OTHER ANTINEOPLASTIC AGENTS
Protein kinase inhibitors
CHEBI has role CHEBI:35610 antineoplastic agent
FDA EPC N0000175605 Kinase Inhibitor
FDA MoA N0000175082 Kinase Inhibitors

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Metastatic malignant melanoma indication 443493003

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 13.38 acidic
pKa2 8.07 Basic

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
EQ 20MG BASE COTELLIC GENENTECH INC N206192 Nov. 10, 2015 RX TABLET ORAL 8362002 Oct. 5, 2026 METHOD OF USING COBIMETINIB FOR THE TREATMENT OF MELANOMA
EQ 20MG BASE COTELLIC GENENTECH INC N206192 Nov. 10, 2015 RX TABLET ORAL 10478400 June 29, 2036 METHOD OF USING COBIMETINIB FOR THE TREATMENT OF MELANOMA
EQ 20MG BASE COTELLIC GENENTECH INC N206192 Nov. 10, 2015 RX TABLET ORAL 10590102 June 30, 2036 METHOD OF USING COBIMETINIB FOR THE TREATMENT OF MELANOMA

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
EQ 20MG BASE COTELLIC GENENTECH INC N206192 Nov. 10, 2015 RX TABLET ORAL Nov. 10, 2020 NEW CHEMICAL ENTITY
EQ 20MG BASE COTELLIC GENENTECH INC N206192 Nov. 10, 2015 RX TABLET ORAL Nov. 10, 2022 FOR THE TREATMENT OF PATIENTS WITH UNRESECTABLE OR METASTATIC MELANOMA WITH BRAF V600E OR V600K MUTATION, IN COMBINATION WITH VEMURAFENIB. COTELLIC IS NOT INDICATED FOR TREATMENT OF PATIENTS WITH WILD-TYPE BRAF MELANOMA

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Dual specificity mitogen-activated protein kinase kinase 1 Kinase INHIBITOR IC50 9.05 SCIENTIFIC LITERATURE SCIENTIFIC LITERATURE
Dual specificity mitogen-activated protein kinase kinase 2 Kinase ALLOSTERIC MODULATOR IC50 6.70 IUPHAR

External reference:

IDSource
D10405 KEGG_DRUG
6EXI96H8SV UNII
1369665-02-0 SECONDARY_CAS_RN
715741000 SNOMEDCT_US
1722365 RXNORM
016576 NDDF
4035069 VANDF
d08396 MMSL
715257001 SNOMEDCT_US
16222096 PUBCHEM_CID
CHEBI:90851 CHEBI
9645 INN_ID
DB05239 DRUGBANK_ID
7626 IUPHAR_LIGAND_ID
CHEMBL2146883 ChEMBL_ID
CHEMBL2364607 ChEMBL_ID
C574276 MESH_SUPPLEMENTAL_RECORD_UI

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Cotellic HUMAN PRESCRIPTION DRUG LABEL 1 50242-717 TABLET, FILM COATED 20 mg ORAL NDA 18 sections