Details of the Drug

General Information of Drug (ID: DM1P6FR)

• Drug Name: ARRY-162
• Synonyms: 606143-89-9; Binimetinib; MEK162; MEK-162; ARRY-438162; 5-[(4-Bromo-2-fluorophenyl)amino]-4-fluoro-N-(2-hydroxyethoxy)-1-methyl-1H-benzimidazole-6-carboxamide; ARRY 162; UNII-181R97MR71; Binimetinib (MEK162, ARRY-162, ARRY-438162); 181R97MR71; MEK162 (ARRY-162, ARRY-438162); 6-(4-bromo-2-fluorophenylamino)-7-fluoro-N-(2-hydroxyethoxy)-3-methyl-3H-benzo[d]imidazole-5-carboxamide; Binimetinib [USAN:INN]; MEK 162; ARRY 438162; MEK162(Binimetinib); Binimetinib (JAN/USAN); D0C4LF; NVP-ME

Indication

Disease Entry	ICD 11	Status	REF
Melanoma	2C30	Approved	[1]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 441.2
  Logarithm of the Partition Coefficient (xlogp); 3.1
  Rotatable Bond Count (rotbonds); 6
  Hydrogen Bond Donor Count (hbonddonor); 3
  Hydrogen Bond Acceptor Count (hbondacc); 7
• ADMET Property:
  Absorption Tmax: The time to maximum plasma concentration (Tmax) is 1.6 h []
  Clearance: The clearance of drug is 20.2 L/h []
  Elimination: Following a single oral dose of 45 mg radiolabeled binimetinib in healthy subjects, 62% (32% unchanged) of the administered dose was recovered in the feces while 31% (6.5% unchanged) was recovered in the urine []
  Half-life: The concentration or amount of drug in body reduced by one-half in 3.5 hours []
  Metabolism: The drug is metabolized via the CYP1A2 and CYP2C19 []
  Vd: The volume of distribution (Vd) of drug is 92 L []
• Chemical Identifiers:
  Formula: C17H15BrF2N4O3
  IUPAC Name: 6-(4-bromo-2-fluoroanilino)-7-fluoro-N-(2-hydroxyethoxy)-3-methylbenzimidazole-5-carboxamide
  Canonical SMILES: CN1C=NC2=C1C=C(C(=C2F)NC3=C(C=C(C=C3)Br)F)C(=O)NOCCO
  InChI: InChI=1S/C17H15BrF2N4O3/c1-24-8-21-16-13(24)7-10(17(26)23-27-5-4-25)15(14(16)20)22-12-3-2-9(18)6-11(12)19/h2-3,6-8,22,25H,4-5H2,1H3,(H,23,26)
  InChIKey: ACWZRVQXLIRSDF-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 10288191
  ChEBI ID: CHEBI:145371
  CAS Number: 606143-89-9
  DrugBank ID: DB11967
  TTD ID: D0C4LF
  VARIDT ID: DR01336
  INTEDE ID: DR0214
  ACDINA ID: D00883

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
ERK activator kinase (MEK)	TTZCRP3	NOUNIPROTAC	Inhibitor	[1]
MAPK/ERK kinase kinase (MAP3K)	TTROQ37	NOUNIPROTAC	Modulator	[2]

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[3]
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[3]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
UDP-glucuronosyltransferase 1A1 (UGT1A1) Main DME	DEYGVN4	UD11_HUMAN	Substrate	[4]
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Substrate	[5]

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from ARRY-162 (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Remdesivir	DMBFZ6L	Moderate	Increased risk of hepatotoxicity by the combination of Arry-162 and Remdesivir.	1D6YCoronavirus Disease 2019 [1D6YCoronavirus Disease 2019]	[6]
Sarecycline	DMLZNIQ	Moderate	Decreased clearance of Arry-162 due to the transporter inhibition by Sarecycline .	Acne vulgaris [ED80]	[6]
Troleandomycin	DMUZNIG	Moderate	Decreased clearance of Arry-162 due to the transporter inhibition by Troleandomycin.	Bacterial infection [1A00-1C4Z]	[6]
Pexidartinib	DMS2J0Z	Major	Increased risk of hepatotoxicity by the combination of Arry-162 and Pexidartinib.	Bone/articular cartilage neoplasm [2F7B]	[7]
Eslicarbazepine	DMZREFQ	Moderate	Increased metabolism of Arry-162 caused by Eslicarbazepine mediated induction of UGT.	Epilepsy/seizure [8A61-8A6Z]	[6]
Avapritinib	DMK2GZX	Major	Increased risk of bleeding by the combination of Arry-162 and Avapritinib.	Gastrointestinal stromal tumour [2B5B]	[8]
Rucaparib	DM9PVX8	Moderate	Decreased clearance of Arry-162 due to the transporter inhibition by Rucaparib.	Ovarian cancer [2C73]	[6]
Darolutamide	DMV7YFT	Moderate	Decreased clearance of Arry-162 due to the transporter inhibition by Darolutamide.	Prostate cancer [2C82]	[6]
Tedizolid	DMG2SKR	Moderate	Decreased clearance of Arry-162 due to the transporter inhibition by Tedizolid.	Skin and skin-structure infection [1F28-1G0Z]	[6]
Fostamatinib	DM6AUHV	Moderate	Decreased clearance of Arry-162 due to the transporter inhibition by Fostamatinib.	Thrombocytopenia [3B64]	[6]
Elagolix	DMB2C0E	Moderate	Decreased clearance of Arry-162 due to the transporter inhibition by Elagolix.	Uterine fibroid [2E86]	[6]

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Carmellose sodium	E00625	Not Available	Disintegrant
Ferric hydroxide oxide yellow	E00539	23320441	Colorant
Ferrosoferric oxide	E00231	14789	Colorant
Lactose monohydrate	E00393	104938	Binding agent; Diluent; Dry powder inhaler carrier; Lyophilization aid
Magnesium stearate	E00208	11177	lubricant
Polyethylene glycol 4000	E00654	Not Available	Coating agent; Diluent; Ointment base; Plasticizing agent; Solvent; Suppository base; lubricant
Polyvinyl alcohol	E00666	Not Available	Coating agent; Emulsion stabilizing agent; Film/Membrane-forming agent
Talc	E00520	16211421	Anticaking agent; Diluent; Glidant; lubricant
Titanium dioxide	E00322	26042	Coating agent; Colorant; Opacifying agent
Hydrophobic colloidal silica	E00285	24261	Anticaking agent; Emulsion stabilizing agent; Glidant; Suspending agent; Viscosity-controlling agent
Cellulose microcrystalline	E00698	Not Available	Adsorbent; Suspending agent; Diluent

Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Binimetinib 15 mg tablet	15 mg	Tablet	Oral

Jump to Detail Pharmaceutical Formulation Page of This Drug

References

• [1] 2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
• [2] MEK and the inhibitors: from bench to bedside. J Hematol Oncol. 2013; 6: 27.
• [3] The impact of P-glycoprotein and breast cancer resistance protein on the brain pharmacokinetics and pharmacodynamics of a panel of MEK inhibitors. Int J Cancer. 2018 Jan 15;142(2):381-391.
• [4] Binimetinib - European Medicines Agency - European Union
• [5] FDA Label of Binimetinib. The 2020 official website of the U.S. Food and Drug Administration.
• [6] Cerner Multum, Inc. "Australian Product Information.".
• [7] Product Information. Turalio (pexidartinib). Daiichi Sankyo, Inc., Parsippany, NJ.
• [8] Cerner Multum, Inc. "UK Summary of Product Characteristics.".