cobimetinib 🐶 Veterinary Use | 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:

DoseUnitRoute
45 mg O

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
S (Water solubility) 0.72 mg/mL Bocci G, Oprea TI, Benet LZ
BDDCS (Biopharmaceutical Drug Disposition Classification System) 1 Bocci G, Oprea TI, Benet LZ

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 169.17 29.57 66 3581 33770 63451605
Skin toxicity 145.40 29.57 37 3610 4677 63480698
Rash maculo-papular 124.16 29.57 52 3595 31844 63453531
Pyrexia 82.60 29.57 117 3530 470361 63015014
Blood creatine phosphokinase increased 80.94 29.57 38 3609 30392 63454983
Chorioretinopathy 76.97 29.57 16 3631 823 63484552
Photosensitivity reaction 73.95 29.57 29 3618 14965 63470410
Diarrhoea 71.58 29.57 138 3509 715228 62770147
Rash 69.75 29.57 119 3528 560752 62924623
Erythema multiforme 65.84 29.57 24 3623 10145 63475230
Stevens-Johnson syndrome 59.75 29.57 29 3618 24921 63460454
Serous retinal detachment 57.87 29.57 11 3636 356 63485019
Toxic skin eruption 50.05 29.57 21 3626 12864 63472511
Retinal detachment 42.05 29.57 15 3632 5954 63479421
Ejection fraction decreased 41.87 29.57 22 3625 22310 63463065
Hypokalaemia 34.81 29.57 36 3611 103768 63381607
Disease progression 33.19 29.57 38 3609 122720 63362655
Enanthema 32.62 29.57 7 3640 419 63484956
Uveitis 31.28 29.57 15 3632 12538 63472837

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 122.21 32.38 45 3682 10549 34942655
Blood creatine phosphokinase increased 96.96 32.38 60 3667 44797 34908407
Serous retinal detachment 94.62 32.38 20 3707 592 34952612
Rash 91.28 32.38 115 3612 222637 34730567
Rash maculo-papular 85.10 32.38 47 3680 28404 34924800
Retinopathy 84.23 32.38 23 3704 2041 34951163
Uveitis 83.17 32.38 31 3696 7504 34945700
Chorioretinopathy 81.75 32.38 21 3706 1472 34951732
Pyrexia 74.13 32.38 129 3598 332884 34620320
Drug reaction with eosinophilia and systemic symptoms 70.88 32.38 44 3683 32968 34920236
Metastases to central nervous system 56.43 32.38 24 3703 8181 34945023
Retinal detachment 55.20 32.38 21 3706 5370 34947834
Diarrhoea 55.14 32.38 125 3602 389787 34563417
Ejection fraction decreased 50.09 32.38 29 3698 19125 34934079
Dermatitis acneiform 48.94 32.38 20 3707 6169 34947035
Skin toxicity 46.70 32.38 18 3709 4766 34948438
Sunburn 46.10 32.38 14 3713 1809 34951395
Hyperthyroidism 44.57 32.38 22 3705 10544 34942660
Pneumonitis 43.73 32.38 33 3694 33845 34919359
Iridocyclitis 38.85 32.38 12 3715 1640 34951564
Intentional product use issue 38.14 32.38 39 3688 59777 34893427
Serous retinopathy 37.33 32.38 7 3720 110 34953094
Acute kidney injury 34.59 32.38 90 3637 304898 34648306
Solar dermatitis 33.66 32.38 6 3721 70 34953134

FDA Adverse Event Reporting System (Geriatric)

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 maculo-papular 195.89 27.52 96 6813 55982 79681497
Drug reaction with eosinophilia and systemic symptoms 195.06 27.52 100 6809 64144 79673335
Blood creatine phosphokinase increased 175.33 27.52 94 6815 65996 79671483
Photosensitivity reaction 172.75 27.52 66 6843 21061 79716418
Skin toxicity 154.45 27.52 48 6861 8266 79729213
Serous retinal detachment 150.40 27.52 31 6878 1003 79736476
Chorioretinopathy 142.05 27.52 34 6875 2197 79735282
Pyrexia 141.89 27.52 228 6681 678481 79058998
Rash 114.78 27.52 190 6719 578168 79159311
Diarrhoea 111.01 27.52 238 6671 880251 78857228
Retinal detachment 109.55 27.52 38 6871 9209 79728270
Uveitis 100.72 27.52 42 6867 16788 79720691
Retinopathy 96.14 27.52 28 6881 3863 79733616
Ejection fraction decreased 85.53 27.52 47 6862 34530 79702949
Dermatitis acneiform 66.79 27.52 27 6882 9966 79727513
Hyperthyroidism 62.78 27.52 33 6876 22176 79715303
Stevens-Johnson syndrome 62.17 27.52 40 6869 39126 79698353
Toxic skin eruption 54.28 27.52 30 6879 22263 79715216
Sunburn 54.22 27.52 18 6891 3815 79733664
Solar dermatitis 51.58 27.52 10 6899 235 79737244
Metastases to central nervous system 51.08 27.52 26 6883 16349 79721130
Erythema multiforme 49.24 27.52 26 6883 17625 79719854
Pneumonitis 48.46 27.52 41 6868 60819 79676660
Colitis 43.78 27.52 42 6867 73265 79664214
Serous retinopathy 42.83 27.52 8 6901 153 79737326
Acute kidney injury 42.12 27.52 119 6790 519285 79218194
Iridocyclitis 39.19 27.52 14 6895 3690 79733789
Myocarditis 39.00 27.52 24 6885 21709 79715770
Rhabdomyolysis 33.58 27.52 43 6866 103088 79634391
Keratoacanthoma 32.49 27.52 9 6900 1036 79736443
Hypokalaemia 31.98 27.52 50 6859 143990 79593489
Electrocardiogram QT prolonged 29.92 27.52 38 6871 90348 79647131
Hepatitis 29.68 27.52 30 6879 55697 79681782
Cholestasis 29.50 27.52 29 6880 52080 79685399
Macular thickening 27.63 27.52 4 6905 13 79737466

FDA Adverse Event Reporting System (Pediatric)

None

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 antineoplastic agents
CHEBI has role CHEBI:79091 MEK inhibitor

Drug Use | Suggest Off label Use Form| |View source of the data|

DiseaseRelationSNOMED_IDDOID
Metastatic malignant melanoma indication 443493003




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

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 11597699 Oct. 5, 2026 AS A SINGLE AGENT FOR THE TREATMENT OF ADULT PATIENTS WITH HISTIOCYTIC NEOPLASMS
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 11087354 June 22, 2034 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
EQ 20MG BASE COTELLIC GENENTECH INC N206192 Nov. 10, 2015 RX TABLET ORAL 11254649 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 July 28, 2025 INFORMATION ADDED TO SECTION 8.4 OF THE LABELING TO INCLUDE THE RESULT OF STUDY GO29665
EQ 20MG BASE COTELLIC GENENTECH INC N206192 Nov. 10, 2015 RX TABLET ORAL Oct. 28, 2025 TREATMENT OF ADULT PATIENTS WITH HISTIOCYTIC NEOPLASMS
EQ 20MG BASE COTELLIC GENENTECH INC N206192 Nov. 10, 2015 RX TABLET ORAL Jan. 28, 2026 PEDIATRIC EXCLUSIVITY
EQ 20MG BASE COTELLIC GENENTECH INC N206192 Nov. 10, 2015 RX TABLET ORAL Oct. 28, 2029 TREATMENT OF ADULT PATIENTS WITH HISTIOCYTIC NEOPLASMS

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
Potassium voltage-gated channel subfamily H member 2 Ion channel IC50 5.36 CHEMBL
Serine/threonine-protein kinase B-raf Kinase IC50 8.74 CHEMBL
Dual specificity mitogen-activated protein kinase kinase 2 Kinase ALLOSTERIC MODULATOR IC50 6.70 IUPHAR
Actin-related protein 3 Unclassified Kd 7.44 CHEMBL

External reference:

IDSource
ER29L26N1X UNII
D10405 KEGG_DRUG
1369665-02-0 SECONDARY_CAS_RN
4035069 VANDF
C4049146 UMLSCUI
CHEBI:90853 CHEBI
VKD PDB_CHEM_ID
CHEMBL2146883 ChEMBL_ID
16222096 PUBCHEM_CID
DB05239 DRUGBANK_ID
CHEMBL3330650 ChEMBL_ID
CHEMBL2364607 ChEMBL_ID
9645 INN_ID
C574276 MESH_SUPPLEMENTAL_RECORD_UI
7626 IUPHAR_LIGAND_ID
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 29 sections
Cotellic HUMAN PRESCRIPTION DRUG LABEL 1 50242-717 TABLET, FILM COATED 20 mg ORAL NDA 29 sections
Cotellic HUMAN PRESCRIPTION DRUG LABEL 1 50242-717 TABLET, FILM COATED 20 mg ORAL NDA 29 sections