binimetinib 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | 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

Approvals:

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

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 584.22 33.17 77 2446 290 63486209
Neoplasm progression 169.36 33.17 61 2462 36367 63450132
Serous retinopathy 121.60 33.17 15 2508 27 63486472
Retinal detachment 82.55 33.17 23 2500 5946 63480553
Colitis 74.48 33.17 37 2486 48491 63438008
Pyrexia 61.76 33.17 84 2439 470394 63016105
Macular detachment 60.19 33.17 9 2514 95 63486404
Off label use 55.56 33.17 97 2426 674365 62812134
Hepatic function abnormal 53.08 33.17 27 2496 37115 63449384
Death 38.96 33.17 60 2463 374321 63112178
Blood creatine phosphokinase increased 37.39 33.17 20 2503 30410 63456089
Second primary malignancy 35.67 33.17 13 2510 7940 63478559
Vision blurred 34.86 33.17 29 2494 91895 63394604
Uveitis 33.22 33.17 14 2509 12539 63473960

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 517.67 30.13 81 2815 531 34953504
Neoplasm progression 176.90 30.13 68 2828 23232 34930803
Serous retinopathy 132.72 30.13 20 2876 97 34953938
Blood creatine phosphokinase increased 56.62 30.13 39 2857 44818 34909217
Second primary malignancy 56.10 30.13 22 2874 7864 34946171
Nausea 43.40 30.13 90 2806 339818 34614217
Vision blurred 42.22 30.13 33 2863 45930 34908105
Dermatitis acneiform 39.60 30.13 16 2880 6173 34947862
Off label use 38.00 30.13 97 2799 419427 34534608
Death 33.91 30.13 90 2806 397959 34556076
Pyrexia 33.24 30.13 80 2816 332933 34621102
Subretinal fluid 30.34 30.13 7 2889 403 34953632

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 1063.79 27.70 158 5263 876 79738091
Neoplasm progression 329.95 27.70 126 5295 51556 79687411
Serous retinopathy 247.58 27.70 35 5386 126 79738841
Blood creatine phosphokinase increased 90.02 27.70 56 5365 66034 79672933
Second primary malignancy 84.27 27.70 33 5388 14317 79724650
Off label use 83.58 27.70 187 5234 907028 78831939
Retinal detachment 82.82 27.70 29 5392 9218 79729749
Death 81.48 27.70 141 5280 566373 79172594
Colitis 77.50 27.70 53 5368 73254 79665713
Pyrexia 75.20 27.70 151 5270 678558 79060409
Vision blurred 72.56 27.70 59 5362 105839 79633128
Dermatitis acneiform 69.50 27.70 26 5395 9967 79729000
Macular detachment 67.90 27.70 12 5409 215 79738752
Hepatic function abnormal 63.73 27.70 47 5374 73060 79665907
Uveitis 59.56 27.70 27 5394 16803 79722164
Nausea 54.54 27.70 165 5256 957031 78781936
Diarrhoea 47.49 27.70 149 5272 880340 78858627
Retinopathy 45.85 27.70 15 5406 3876 79735091
Liver disorder 40.64 27.70 36 5385 72381 79666586
Disease progression 37.57 27.70 54 5367 184308 79554659
Detachment of retinal pigment epithelium 36.87 27.70 9 5412 807 79738160
Subretinal fluid 36.69 27.70 9 5412 823 79738144
Decreased appetite 36.28 27.70 75 5346 342343 79396624
Large intestinal ulcer 35.25 27.70 13 5408 4784 79734183
Demyelinating polyneuropathy 34.58 27.70 10 5411 1716 79737251
Hepatic cytolysis 34.40 27.70 22 5399 27129 79711838
Macular oedema 33.58 27.70 13 5408 5461 79733506
Alanine aminotransferase increased 32.21 27.70 47 5374 162523 79576444
Hospice care 31.65 27.70 15 5406 10309 79728658
Visual impairment 31.56 27.70 35 5386 92096 79646871
Retinal oedema 30.50 27.70 8 5413 957 79738010
Underdose 30.42 27.70 22 5399 33129 79705838

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 agents
CHEBI has role CHEBI:68495 Type I cell-death inducers
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
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 8193229 March 13, 2023 METHOD OF TREATING MELANOMA
15MG MEKTOVI ARRAY BIOPHARMA INC N210498 June 27, 2018 RX TABLET ORAL 8513293 March 13, 2023 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 INDICATED IN COMBINATION WITH ENCORAFENIB FOR THE TREATMENT OF MELANOMA
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 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 June 27, 2023 NEW CHEMICAL ENTITY
15MG MEKTOVI ARRAY BIOPHARMA INC N210498 June 27, 2018 RX TABLET ORAL June 27, 2025 ENCORAFENIB IS INDICATED IN COMBINATION WITH BINIMETINIB, FOR THE TREATMENT OF PATIENTS WITH UNRESECTABLE OR METASTATIC MELANOMA WITH A BRAF V600E OR V600K 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
C3899947 UMLSCUI
CHEBI:145371 CHEBI
QO7 PDB_CHEM_ID
CHEMBL3187723 ChEMBL_ID
10288191 PUBCHEM_CID
DB11967 DRUGBANK_ID
D10604 KEGG_DRUG
9764 INN_ID
7921 IUPHAR_LIGAND_ID
283903 MMSL
34461 MMSL
d08818 MMSL
017616 NDDF
772095008 SNOMEDCT_US
772195005 SNOMEDCT_US
4037645 VANDF
2049122 RXNORM
C581313 MESH_SUPPLEMENTAL_RECORD_UI

Pharmaceutical products:

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