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 151.26 28.45 60 2859 29488 46653655
Rash 84.39 28.45 107 2812 356405 46326738
Rash maculo-papular 84.20 28.45 39 2880 27835 46655308
Pyrexia 66.05 28.45 94 2825 348708 46334435
Chorioretinopathy 66.03 28.45 14 2905 727 46682416
Skin toxicity 65.29 28.45 19 2900 3635 46679508
Photosensitivity reaction 61.96 28.45 25 2894 12767 46670376
Diarrhoea 61.64 28.45 118 2801 559484 46123659
Erythema multiforme 61.30 28.45 23 2896 9681 46673462
Serous retinal detachment 60.87 28.45 10 2909 124 46683019
Blood creatine phosphokinase increased 57.40 28.45 30 2889 27694 46655449
Stevens-Johnson syndrome 47.62 28.45 25 2894 23272 46659871
Toxic skin eruption 45.86 28.45 20 2899 12367 46670776
Retinal detachment 39.30 28.45 14 2905 5086 46678057
Ejection fraction decreased 35.94 28.45 19 2900 17918 46665225
Enanthema 31.48 28.45 7 2912 454 46682689
Hypokalaemia 29.96 28.45 32 2887 87992 46595151
Uveitis 28.92 28.45 13 2906 8628 46674515

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
Photosensitivity reaction 107.81 32.10 40 3129 9654 29939655
Serous retinal detachment 95.98 32.10 18 3151 286 29949023
Blood creatine phosphokinase increased 81.11 32.10 53 3116 43795 29905514
Rash 79.15 32.10 99 3070 191790 29757519
Uveitis 77.41 32.10 27 3142 5450 29943859
Retinopathy 75.73 32.10 21 3148 1989 29947320
Chorioretinopathy 67.95 32.10 18 3151 1434 29947875
Rash maculo-papular 62.88 32.10 37 3132 25381 29923928
Pyrexia 57.10 32.10 107 3062 294382 29654927
Ejection fraction decreased 56.65 32.10 29 3140 15146 29934163
Diarrhoea 55.83 32.10 114 3055 333989 29615320
Retinal detachment 53.01 32.10 20 3149 5040 29944269
Metastases to central nervous system 49.24 32.10 21 3148 7263 29942046
Drug reaction with eosinophilia and systemic symptoms 49.13 32.10 33 3136 28455 29920854
Sunburn 47.54 32.10 14 3155 1642 29947667
Hyperthyroidism 40.79 32.10 19 3150 8079 29941230
Intentional product use issue 39.70 32.10 32 3137 36408 29912901
Pneumonitis 33.98 32.10 26 3143 27428 29921881
Dermatitis acneiform 33.87 32.10 15 3154 5674 29943635
Solar dermatitis 33.86 32.10 6 3163 68 29949241
Acute kidney injury 32.73 32.10 82 3087 273760 29675549
Iridocyclitis 32.22 32.10 10 3159 1399 29947910

Pharmacologic Action:

SourceCodeDescription
ATC L01EE02 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
PROTEIN KINASE INHIBITORS
Mitogen-activated protein kinase (MEK) inhibitors
FDA MoA N0000175082 Kinase Inhibitors
FDA EPC N0000175605 Kinase Inhibitor
CHEBI has role CHEBI:35610 cytostatic
CHEBI has role CHEBI:79091 mitogen-activated protein 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)

None

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, 2022 FOR THE TREATMENT OF PATIENTS WITH UNRESECTABLE OR METASTATIC MELANOMA WITH BRAF V600E OR V600K MUTATION, IN COMBINULLTION 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
1369665-02-0 SECONDARY_CAS_RN
4035069 VANDF
C4049146 UMLSCUI
CHEBI:90853 CHEBI
VKD PDB_CHEM_ID
CHEMBL2146883 ChEMBL_ID
CHEMBL2364607 ChEMBL_ID
DB05239 DRUGBANK_ID
C574276 MESH_SUPPLEMENTAL_RECORD_UI
16222096 PUBCHEM_CID
7626 IUPHAR_LIGAND_ID
9645 INN_ID
ER29L26N1X UNII
1722365 RXNORM
237126 MMSL
31291 MMSL
d08396 MMSL
016576 NDDF
016577 NDDF
715257001 SNOMEDCT_US
715741000 SNOMEDCT_US
734511001 SNOMEDCT_US

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Cotellic HUMAN PRESCRIPTION DRUG LABEL 1 50242-717 TABLET, FILM COATED 20 mg ORAL NDA 28 sections