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

Stem definitionDrug idCAS RN
tyrosine kinase inhibitors 5290 606143-89-9

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • binimetinib
  • mektovi
  • MEK162
  • ARRY-162
  • ARRY-438162
Binimetinib is a reversible inhibitor of mitogen-activated extracellular signal regulated kinase 1 (MEK1) and MEK2 activity. MEK proteins are upstream regulators of the extracellular signal-related kinase (ERK) pathway. In vitro, binimetinib inhibited extracellular signal-related kinase (ERK) phosphorylation in cellfree assays as well as viability and MEK-dependent phosphorylation of BRAF-mutant human melanoma cell lines. Binimetinib also inhibited in vivo ERK phosphorylation and tumor growth in BRAF-mutant murine xenograft models.
  • Molecular weight: 441.23
  • Formula: C17H15BrF2N4O3
  • CLOGP: 3.16
  • LIPINSKI: 0
  • HAC: 7
  • HDO: 3
  • TPSA: 88.41
  • ALOGS: -3.95
  • ROTB: 6
  • Status: ONP
    • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
90 mg O

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 1 Bocci G, Oprea TI, Benet LZ
BA (Bioavailability) 0.71 % Kawashima H, Watanabe R, Esaki T, Kuroda M, Nagao C, Natsume-Kitatani Y, Ohashi R, Komura H, Mizuguchi K

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 2.088 High 1
caco2-efflux Caco-2 efflux ratio (BA/AB) 13.677 High 1
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 19.143 10^-6 cm/s High 1
dh-clint Dog hepatocyte intrinsic clearance 2.897 uL/min/10^6 cells High 1
dppb Dog plasma protein binding (% unbound) 10.730 % High 1
fcs-ppb Fetal calf serum protein binding (% unbound) 19.100 % High 1
herg hERG pIC50 4.512 pIC50 High 1
hh-clint Human hepatocyte intrinsic clearance 1.905 uL/min/10^6 cells High 1
hlm-clint Human liver microsomal intrinsic clearance 5.534 uL/min/mg protein High 1
hppb Human plasma protein binding (% unbound) 7.250 % High 1
kinase-safety-class ABL2,ACVR2B,ALK,AURKA,AXL,BLK,BMX,BRAF,BTK,CAMK2B,CAMK2D,CDK1,CDK14,CDK16,CDK19,CDK2,CDK4,CDK5,CDK6,CDK7,CDK9,CLK4,CSF1R,DDR1,DYRK1B,EGFR,EPHA2,EPHB4,ERBB2,ERBB4,FGFR1,FLT1,FLT3,FYN,GAK,GRK2,GSK3B,IRAK1,ITK,JAK1,KDR,KIT,LCK,LYN,MAP2K1,MAP3K10,MAP3K21,MAP3K7,MAP4K1,MAP4K3,MAP4K5,MAPK1,MAPK11,MAPK14,MAPK7,MAPK9,MARK4,MET,NTRK1,PDGFRB,PDK1,PDK2,PDK4,PIK3CA,PIK3CB,PIK3CD,PIK3CG,PRKCD,PRKDC,RET,SIK2,SIK3,SRC,STK33,SYK,TEK,TGFBR1,TTK,ULK1,ULK2,YES1 81
kinase-selectivity-class ACVR2B,AURKA,AXL,BRAF,CAMK2D,CDK9,CSF1R,DDR1,EGFR,EPHB4,ERBB2,FLT1,FYN,GRK2,JAK1,KDR,KIT,LCK,LYN,MAP2K1,MAP3K21,MAP4K1,MAP4K3,MAPK1,MAPK7,MARK4,PRKCD,SIK2,SIK3,STK33,SYK,ULK1,YES1 33
mdck-mdr1-bcrp-efflux MDCK-MDR1-BCRP efflux ratio 31.333 High 0.85
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 23.496 High 1
mh-clint Mouse hepatocyte intrinsic clearance 17.338 High 1
mppb Mouse plasma protein binding (% unbound) 9.700 High 1
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 38.994 High 1
pfas-class PFAS structural alert (1 = True, 0 = False) 0
pppb Pig plasma protein binding (% unbound) 15.250 % High 1
rat-kpuu-brain Rat brain Kpuu 0.021 % High 0.85
rh-clint Rat hepatocyte intrinsic clearance 7.379 uL/min/10^6 cells High 1
rh-fuinc Rat hepatocyte fraction unbound in incubation 63.900 % High 1
rppb Rat plasma protein binding (% unbound) 7.890 % High 1
solubility-dd Solubility at pH 7.4 in DMSO 31.696 uM High 1

Approvals:

DateAgencyCompanyOrphan
Jan. 8, 2019 PMDA ONO PHARMACEUTICAL CO., LTD.
June 27, 2018 FDA ARRAY BIOPHARMA INC
Sept. 20, 2018 EMA Pierre Fabre Medicament

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
Serous retinal detachment 977.71 30.28 134 4712 500 90623101
Neoplasm progression 262.28 30.28 96 4750 44390 90579211
Retinal detachment 134.42 30.28 37 4809 6785 90616816
Off label use 122.11 30.28 213 4633 1102039 89521562
Colitis 119.02 30.28 63 4783 69879 90553722
Serous retinopathy 107.70 30.28 14 4832 30 90623571
Pyrexia 97.81 30.28 146 4700 660339 89963262
Nausea 81.69 30.28 181 4665 1110135 89513466
Death 76.24 30.28 107 4739 456444 90167157
Vision blurred 76.20 30.28 56 4790 110237 90513364
Blood creatine phosphokinase increased 67.48 30.28 34 4812 33989 90589612
Hepatic function abnormal 65.67 30.28 37 4809 46251 90577350
Diarrhoea 59.91 30.28 145 4701 939045 89684556
Retinopathy 59.71 30.28 17 4829 3517 90620084
Macular oedema 58.40 30.28 18 4828 4891 90618710
Macular detachment 57.18 30.28 9 4837 99 90623502
Malignant neoplasm progression 55.82 30.28 46 4800 106824 90516777
Tumour lysis syndrome 54.43 30.28 21 4825 11131 90612470
Uveitis 50.47 30.28 22 4824 15881 90607720
Large intestinal ulcer 49.30 30.28 15 4831 3902 90619699
Second primary malignancy 45.21 30.28 18 4828 10360 90613241
Decreased appetite 44.08 30.28 75 4771 376465 90247136
Detachment of retinal pigment epithelium 43.32 30.28 9 4837 496 90623105
Dermatitis acneiform 42.18 30.28 15 4831 6339 90617262
Drug ineffective 37.08 30.28 14 4832 1384284 89239317
Alanine aminotransferase increased 36.55 30.28 38 4808 118300 90505301
Visual impairment 36.47 30.28 40 4806 132325 90491276
Immune-mediated hepatitis 35.88 30.28 11 4835 2933 90620668
Vomiting 35.27 30.28 107 4739 788186 89835415
Colour blindness acquired 33.64 30.28 6 4840 146 90623455
Hepatic cytolysis 31.55 30.28 20 4826 30896 90592705
Ocular toxicity 31.54 30.28 8 4838 1069 90622532

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
Serous retinal detachment 805.31 24.47 133 5121 811 42615270
Neoplasm progression 268.14 24.47 109 5145 28891 42587190
Serous retinopathy 143.99 24.47 25 5229 211 42615870
Second primary malignancy 88.33 24.47 36 5218 9539 42606542
Blood creatine phosphokinase increased 77.93 24.47 57 5197 48281 42567800
Death 64.34 24.47 163 5091 471022 42145059
Off label use 62.90 24.47 196 5058 638139 41977942
Pyrexia 61.94 24.47 144 5110 393898 42222183
Nausea 60.18 24.47 143 5111 396656 42219425
Vision blurred 55.88 24.47 49 5205 53650 42562431
Dermatitis acneiform 54.41 24.47 24 5230 7715 42608366
Visual impairment 50.27 24.47 42 5212 43071 42573010
Fatigue 45.68 24.47 137 5117 435504 42180577
Malignant neoplasm progression 45.20 24.47 61 5193 108339 42507742
Retinal detachment 45.11 24.47 20 5234 6505 42609576
Retinopathy 44.95 24.47 15 5239 2266 42613815
Macular oedema 41.96 24.47 16 5238 3553 42612528
Subretinal fluid 41.77 24.47 11 5243 732 42615349
Colitis 39.66 24.47 38 5216 46534 42569547
Uveitis 38.45 24.47 20 5234 9238 42606843
Diarrhoea 38.38 24.47 134 5120 460715 42155366
Detachment of retinal pigment epithelium 34.15 24.47 9 5245 601 42615480
Metastases to central nervous system 33.61 24.47 19 5235 10336 42605745
Liver disorder 33.09 24.47 32 5222 39612 42576469
Retinal oedema 30.04 24.47 9 5245 959 42615122
Hepatitis 26.56 24.47 24 5230 27276 42588805
Transient acantholytic dermatosis 25.32 24.47 6 5248 259 42615822
Large intestinal ulcer 25.26 24.47 10 5244 2453 42613628
Cystoid macular oedema 25.26 24.47 8 5246 1025 42615056
Renal impairment 25.02 24.47 47 5207 110181 42505900
Hepatic cytolysis 24.94 24.47 23 5231 26821 42589260

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
Serous retinal detachment 1721.72 24.19 265 9596 1407 110578031
Neoplasm progression 506.49 24.19 197 9664 64398 110515040
Serous retinopathy 219.31 24.19 35 9826 240 110579198
Death 164.26 24.19 252 9609 698617 109880821
Off label use 161.21 24.19 387 9474 1499798 109079640
Retinal detachment 151.17 24.19 51 9810 11049 110568389
Blood creatine phosphokinase increased 145.32 24.19 87 9774 72990 110506448
Colitis 127.76 24.19 91 9770 102232 110477206
Second primary malignancy 126.94 24.19 51 9810 18017 110561421
Vision blurred 125.98 24.19 99 9762 128923 110450515
Pyrexia 125.52 24.19 258 9603 898007 109681431
Nausea 109.49 24.19 297 9564 1235393 109344045
Retinopathy 104.70 24.19 31 9830 4398 110575040
Dermatitis acneiform 103.81 24.19 40 9821 12655 110566783
Malignant neoplasm progression 90.91 24.19 94 9767 174473 110404965
Macular oedema 90.88 24.19 31 9830 6935 110572503
Diarrhoea 84.34 24.19 257 9604 1139248 109440190
Uveitis 80.12 24.19 39 9822 21671 110557767
Hepatic function abnormal 75.43 24.19 63 9798 89232 110490206
Visual impairment 72.88 24.19 74 9787 134354 110445084
Detachment of retinal pigment epithelium 67.06 24.19 16 9845 989 110578449
Large intestinal ulcer 64.98 24.19 23 9838 5738 110573700
Macular detachment 63.21 24.19 12 9849 244 110579194
Subretinal fluid 62.44 24.19 16 9845 1328 110578110
Decreased appetite 59.51 24.19 131 9730 475715 110103723
Retinal oedema 59.41 24.19 16 9845 1611 110577827
Hepatic cytolysis 55.30 24.19 43 9818 55010 110524428
Drug ineffective 52.35 24.19 36 9825 1520504 109058934
Alanine aminotransferase increased 49.64 24.19 71 9790 183702 110395736
Metastases to central nervous system 47.48 24.19 28 9833 22789 110556649
Lipase increased 47.15 24.19 26 9835 18646 110560792
Tumour lysis syndrome 46.92 24.19 31 9830 30770 110548668
Renal impairment 46.83 24.19 70 9791 188375 110391063
Aspartate aminotransferase increased 46.47 24.19 64 9797 159872 110419566
Colour blindness acquired 43.11 24.19 8 9853 143 110579295
Fatigue 41.20 24.19 215 9646 1215743 109363695
Liver disorder 39.94 24.19 56 9805 142187 110437251
Cystoid macular oedema 38.64 24.19 13 9848 2787 110576651
Immune-mediated enterocolitis 36.68 24.19 18 9843 10167 110569271
Myalgia 35.75 24.19 68 9793 222313 110357125
Vomiting 35.00 24.19 167 9694 910508 109668930
Immune-mediated hepatitis 33.93 24.19 15 9846 6696 110572742
Demyelinating polyneuropathy 33.26 24.19 11 9850 2238 110577200
Gamma-glutamyltransferase increased 30.05 24.19 32 9829 61277 110518161
Rash maculo-papular 29.95 24.19 35 9826 74187 110505251
Eye symptom 29.14 24.19 6 9855 187 110579251
Hypothyroidism 28.79 24.19 34 9827 72865 110506573
Enterocolitis 28.68 24.19 19 9842 18930 110560508
Metamorphopsia 28.27 24.19 9 9852 1624 110577814
Eye disorder 27.77 24.19 22 9839 28884 110550554
Underdose 27.38 24.19 31 9830 63523 110515915
Melanocytic naevus 26.55 24.19 12 9849 5642 110573796
Skin toxicity 25.94 24.19 15 9846 11768 110567670
Disease progression 25.82 24.19 63 9798 243971 110335467
Hospice care 25.15 24.19 15 9846 12458 110566980
Blood lactate dehydrogenase increased 25.09 24.19 25 9836 44309 110535129
Blood creatinine increased 24.67 24.19 52 9809 182837 110396601
Pneumonitis 24.31 24.19 32 9829 76499 110502939
Joint swelling 24.22 24.19 5 9856 442840 110136598

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC L01EE03 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
PROTEIN KINASE INHIBITORS
Mitogen-activated protein kinase (MEK) inhibitors
CHEBI has role CHEBI:35610 antineoplastic agent
CHEBI has role CHEBI:35842 antirheumatic drug
CHEBI has role CHEBI:68495 apoptosis inducer
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
cobimetinibmirdametinibselumetinibtrametinib

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

DiseaseRelationSNOMED_IDDOID
Metastatic malignant melanoma indication 443493003
Unresectable malignant melanoma with BRAF gene mutation indication 830150003
BRAF mutation-positive colorectal cancer indication




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 8.84 acidic
pKa2 4.05 Basic

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
15MG MEKTOVI ARRAY BIOPHARMA INC N210498 June 27, 2018 RX TABLET ORAL 10005761 Aug. 27, 2030 INDICATED IN COMBINATION WITH ENCORAFENIB FOR THE TREATMENT OF MELANOMA
15MG MEKTOVI ARRAY BIOPHARMA INC N210498 June 27, 2018 RX TABLET ORAL 10005761 Aug. 27, 2030 MEKTOVI IS A KINASE INHIBITOR INDICATED IN COMBINATION WITH ENCORAFENIB, FOR THE TREATMENT OF PATIENTS WITH METASTATIC NON SMALL CELL LUNG CANCER WITH A BRAF V600E MUTATION, AS DETECTED BY AN FDA-APPROVED TEST
15MG MEKTOVI ARRAY BIOPHARMA INC N210498 June 27, 2018 RX TABLET ORAL 9850229 Aug. 27, 2030 INDICATED IN COMBINATION WITH ENCORAFENIB FOR THE TREATMENT OF MELANOMA WITH A BRAF MUTATION
15MG MEKTOVI ARRAY BIOPHARMA INC N210498 June 27, 2018 RX TABLET ORAL 9314464 July 4, 2031 INDICATED IN COMBINATION WITH ENCORAFENIB FOR THE TREATMENT OF MELANOMA MEDIATED BY A B-RAF PROTEIN KINASE
15MG MEKTOVI ARRAY BIOPHARMA INC N210498 June 27, 2018 RX TABLET ORAL 9314464 July 4, 2031 MEKTOVI IS A KINASE INHIBITOR INDICATED IN COMBINATION WITH ENCORAFENIB, FOR THE TREATMENT OF PATIENTS WITH METASTATIC NON SMALL CELL LUNG CANCER WITH A BRAF V600E MUTATION, AS DETECTED BY AN FDA-APPROVED TEST
15MG MEKTOVI ARRAY BIOPHARMA INC N210498 June 27, 2018 RX TABLET ORAL 9598376 Oct. 18, 2033 METHOD OF TREATING MELANOMA
15MG MEKTOVI ARRAY BIOPHARMA INC N210498 June 27, 2018 RX TABLET ORAL 9980944 Oct. 18, 2033 TREATMENT OF MELANOMA WITH A BRAF MUTATION

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
15MG MEKTOVI ARRAY BIOPHARMA INC N210498 June 27, 2018 RX TABLET ORAL Oct. 11, 2026 ENCORAFENIB IN COMBINATION WITH BINIMETINIB, IS INDICATED FOR THE TREATMENT OF ADULT PATIENTS WITH METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC) WITH BRAF V600E MUTATION, AS DETECTED BY AN FDA-APPROVED TEST

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])		Mechanism
action		Bioact sourceMoA source
Dual specificity mitogen-activated protein kinase kinase 1 Kinase INHIBITOR IC50 7.90 IUPHAR DRUG LABEL
Dual specificity mitogen-activated protein kinase kinase 2 Kinase INHIBITOR IC50 7.90 IUPHAR DRUG LABEL
Ribosyldihydronicotinamide dehydrogenase [quinone] Enzyme Kd 4.83 CHEMBL

External reference:

IDSource
181R97MR71 UNII
4037645 VANDF
C3899947 UMLSCUI
CHEBI:145371 CHEBI
QO7 PDB_CHEM_ID
CHEMBL3187723 ChEMBL_ID
10288191 PUBCHEM_CID
DB11967 DRUGBANK_ID
D10604 KEGG_DRUG
9764 INN_ID
C581313 MESH_SUPPLEMENTAL_RECORD_UI
7921 IUPHAR_LIGAND_ID
772095008 SNOMEDCT_US
772195005 SNOMEDCT_US
283903 MMSL
34461 MMSL
d08818 MMSL
017616 NDDF
2049122 RXNORM
181R97MR71 INXIGHT DRUGS

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
MEKTOVI HUMAN PRESCRIPTION DRUG LABEL 1 70255-010 TABLET, FILM COATED 15 mg ORAL NDA 29 sections