cobimetinib 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | 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

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 2.610 High 0.80
caco2-efflux Caco-2 efflux ratio (BA/AB) 23.442 High 0.80
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 7.925 10^-6 cm/s High 0.80
dh-clint Dog hepatocyte intrinsic clearance 5.105 uL/min/10^6 cells High 0.80
dppb Dog plasma protein binding (% unbound) 3.610 % High 0.80
fcs-ppb Fetal calf serum protein binding (% unbound) 7.280 % High 0.80
herg hERG pIC50 5.381 pIC50 High 0.80
hh-clint Human hepatocyte intrinsic clearance 4.645 uL/min/10^6 cells High 0.80
hlm-clint Human liver microsomal intrinsic clearance 26.002 uL/min/mg protein High 0.80
hppb Human plasma protein binding (% unbound) 4.220 % High 0.80
kinase-safety-class ACVR2A,ACVR2B,ALK,AURKA,AXL,BRAF,BTK,CAMK2B,CAMK2D,CDK5,CDK9,CSF1R,DDR1,DYRK1B,EGFR,EPHB4,ERBB2,FLT3,GAK,GRK2,GSK3B,ITK,JAK1,MAP2K1,MAP2K6,MAP3K21,MAP4K1,MAPK1,MAPK11,MAPK14,MAPK7,MAPK9,MAPKAPK2,MARK4,MET,PDK1,PDK2,PDK4,PIK3CA,PIK3CB,PIK3CD,PIK3CG,PRKCD,PRKDC,SIK2,SIK3,STK33,SYK,TEK,TTK,ULK1 51
kinase-selectivity-class ACVR2B,AURKA,AXL,BRAF,CAMK2D,CDK9,CSF1R,DDR1,GRK2,JAK1,MAP2K1,MAP2K6,MAP3K21,MAP4K1,MAP4K3,MAPK1,MAPK7,PRKCD,SIK2,SIK3,STK33,SYK,ULK1 23
mdck-mdr1-bcrp-efflux MDCK-MDR1-BCRP efflux ratio 15.560 Moderate 0.73
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 24.831 High 0.80
mh-clint Mouse hepatocyte intrinsic clearance 15.922 High 0.80
mppb Mouse plasma protein binding (% unbound) 3.760 High 0.80
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 94.624 High 0.80
pfas-class PFAS structural alert (1 = True, 0 = False) 0
pppb Pig plasma protein binding (% unbound) 8.680 % High 0.80
rat-kpuu-brain Rat brain Kpuu 0.017 % Moderate 0.73
rh-clint Rat hepatocyte intrinsic clearance 24.099 uL/min/10^6 cells High 0.80
rh-fuinc Rat hepatocyte fraction unbound in incubation 19.030 % High 0.80
rppb Rat plasma protein binding (% unbound) 4.290 % High 0.80
solubility-dd Solubility at pH 7.4 in DMSO 644.169 uM High 0.80

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
Skin toxicity 203.58 30.30 50 4194 6729 90617474
Drug reaction with eosinophilia and systemic symptoms 170.70 30.30 67 4177 42691 90581512
Rash maculo-papular 128.51 30.30 54 4190 40879 90583324
Photosensitivity reaction 104.31 30.30 37 4207 17770 90606433
Pyrexia 100.69 30.30 138 4106 660347 89963856
Blood creatine phosphokinase increased 87.47 30.30 39 4205 33984 90590219
Diarrhoea 81.88 30.30 152 4092 939038 89685165
No adverse event 80.25 30.30 46 4198 67936 90556267
Rash 74.54 30.30 133 4111 795967 89828236
Chorioretinopathy 73.53 30.30 15 4229 865 90623338
Erythema multiforme 70.02 30.30 25 4219 12221 90611982
Stevens-Johnson syndrome 60.87 30.30 29 4215 29347 90594856
Dermatitis acneiform 60.32 30.30 19 4225 6335 90617868
Serous retinal detachment 54.11 30.30 11 4233 623 90623580
Disease progression 51.61 30.30 49 4195 156566 90467637
Toxic skin eruption 50.08 30.30 21 4223 15753 90608450
Retinal detachment 43.08 30.30 15 4229 6807 90617396
Ejection fraction decreased 42.74 30.30 22 4222 26231 90597972
Hypokalaemia 37.53 30.30 38 4206 131078 90493125
Metastases to central nervous system 35.36 30.30 17 4227 17525 90606678
Enanthema 32.79 30.30 7 4237 503 90623700
Uveitis 30.81 30.30 15 4229 15888 90608315

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 129.54 31.59 48 4065 12654 42604568
Blood creatine phosphokinase increased 103.47 31.59 62 4051 48276 42568946
Rash 102.08 31.59 129 3984 276825 42340397
Serous retinal detachment 98.86 31.59 22 4091 922 42616300
Rash maculo-papular 90.49 31.59 52 4061 37451 42579771
Retinopathy 84.21 31.59 23 4090 2258 42614964
Pyrexia 83.12 31.59 141 3972 393901 42223321
Uveitis 79.95 31.59 31 4082 9227 42607995
Chorioretinopathy 78.36 31.59 20 4093 1511 42615711
No adverse event 73.11 31.59 46 4067 38975 42578247
Dermatitis acneiform 70.70 31.59 27 4086 7712 42609510
Skin toxicity 67.65 31.59 25 4088 6524 42610698
Drug reaction with eosinophilia and systemic symptoms 67.51 31.59 45 4068 42030 42575192
Diarrhoea 59.26 31.59 134 3979 460715 42156507
Ejection fraction decreased 56.93 31.59 32 4081 22055 42595167
Metastases to central nervous system 53.36 31.59 24 4089 10331 42606891
Retinal detachment 53.33 31.59 21 4092 6504 42610718
Sunburn 49.69 31.59 15 4098 2100 42615122
Hyperthyroidism 43.08 31.59 23 4090 14318 42602904
Pneumonitis 40.55 31.59 33 4080 41685 42575537
Serous retinopathy 38.92 31.59 8 4105 228 42616994
Iridocyclitis 36.59 31.59 12 4101 2199 42615023
Intentional product use issue 35.43 31.59 39 4074 71794 42545428
Solar dermatitis 33.51 31.59 6 4107 80 42617142

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
Skin toxicity 219.16 25.43 65 7771 11718 110569745
Photosensitivity reaction 210.08 25.43 76 7760 25513 110555950
Rash maculo-papular 209.27 25.43 103 7733 74119 110507344
Drug reaction with eosinophilia and systemic symptoms 196.56 25.43 102 7734 81993 110499470
Blood creatine phosphokinase increased 192.96 25.43 97 7739 72980 110508483
Pyrexia 169.19 25.43 258 7578 898007 109683456
Serous retinal detachment 152.96 25.43 33 7803 1639 110579824
Chorioretinopathy 137.26 25.43 32 7804 2263 110579200
Diarrhoea 125.69 25.43 259 7577 1139246 109442217
Rash 124.50 25.43 214 7622 820750 109760713
Dermatitis acneiform 116.60 25.43 41 7795 12654 110568809
Retinal detachment 110.23 25.43 38 7798 11062 110570401
Uveitis 98.54 25.43 42 7794 21668 110559795
Retinopathy 98.11 25.43 28 7808 4401 110577062
Ejection fraction decreased 95.46 25.43 50 7786 40830 110540633
No adverse event 86.94 25.43 58 7778 73781 110507682
Hyperthyroidism 63.24 25.43 34 7802 29227 110552236
Stevens-Johnson syndrome 62.93 25.43 40 7796 46861 110534602
Metastases to central nervous system 62.23 25.43 31 7805 22786 110558677
Sunburn 58.81 25.43 19 7817 4529 110576934
Toxic skin eruption 54.01 25.43 30 7806 27485 110553978
Solar dermatitis 52.92 25.43 10 7826 252 110581211
Erythema multiforme 52.67 25.43 27 7809 21070 110560393
Serous retinopathy 52.43 25.43 10 7826 265 110581198
Pneumonitis 49.49 25.43 42 7794 76489 110504974
Acute kidney injury 47.05 25.43 124 7712 635306 109946157
Disease progression 46.76 25.43 71 7765 243963 110337500
Colitis 42.68 25.43 44 7792 102279 110479184
Rhabdomyolysis 36.79 25.43 44 7792 120357 110461106
Iridocyclitis 36.77 25.43 14 7822 5394 110576069
Myocarditis 33.89 25.43 23 7813 30032 110551431
Hypokalaemia 33.40 25.43 52 7784 182396 110399067
Keratoacanthoma 31.38 25.43 9 7827 1439 110580024
Electrocardiogram QT prolonged 30.34 25.43 38 7798 108922 110472541
Cholestasis 29.19 25.43 29 7807 64489 110516974
Autoimmune colitis 28.57 25.43 9 7827 1976 110579487
Hepatocellular injury 27.15 25.43 25 7811 50617 110530846
Transaminases increased 25.95 25.43 27 7809 63363 110518100

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 agent
CHEBI has role CHEBI:79091 EC 2.7.11.24 (mitogen-activated protein kinase) inhibitor

Related Drugs by ATC class:

L01EE Mitogen-activated protein kinase (MEK) inhibitors 4 drugs
binimetinibmirdametinibselumetinibtrametinib

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 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 Structural 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
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
ER29L26N1X INXIGHT DRUGS

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Cotellic HUMAN PRESCRIPTION DRUG LABEL 1 50242-717 TABLET, FILM COATED 20 mg ORAL NDA 29 sections