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Details

Stereochemistry ACHIRAL
Molecular Formula C17H15BrF2N4O3
Molecular Weight 441.227
Optical Activity UNSPECIFIED
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of BINIMETINIB

SMILES

CN1C=NC2=C1C=C(C(=O)NOCCO)C(NC3=C(F)C=C(Br)C=C3)=C2F

InChI

InChIKey=ACWZRVQXLIRSDF-UHFFFAOYSA-N
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)

HIDE SMILES / InChI

Molecular Formula C17H15BrF2N4O3
Molecular Weight 441.227
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description

Binimetinib (MEK162) is an oral small-molecule with potential antineoplastic activity. It is a selective mitogen-activated protein kinase 1 and 2 (MEK1/2) inhibitor, a key protein kinase in the RAS/RAF/MEK/ERK pathway, which regulates several key cellular activities including proliferation, differentiation, migration, survival and angiogenesis. Inappropriate activation of this pathway has been shown to occur in many cancers, in particular through mutations in BRAF, KRAS and NRAS. MEK162 at 6 mg/kg, BID combined with BEZ235 (dual PI3K/mTOR inhibitor) resulted in a significant reduction of tumor growth in immunodeficient mice injected with MCF7 cells. There are three ongoing Phase 3 trials with binimetinib in advanced cancer patients: NEMO (NRAS-mutant melanoma), COLUMBUS (encorafenib in combination with binimetinib in BRAF-mutant melanoma) and BEACON CRC (encorafenib, binimetinib and cetuximab in BRAF-mutant colorectal cancer).

CNS Activity

Originator

Approval Year

PubMed

PubMed

TitleDatePubMed
MEK and the inhibitors: from bench to bedside.
2013 Apr 12
RSK3/4 mediate resistance to PI3K pathway inhibitors in breast cancer.
2013 Jun
MEK162 for patients with advanced melanoma harbouring NRAS or Val600 BRAF mutations: a non-randomised, open-label phase 2 study.
2013 Mar
Adjuvant immunotherapy of melanoma and development of new approaches using the neoadjuvant approach.
2013 May-Jun
MEK1/2 inhibitors in the treatment of gynecologic malignancies.
2014 Apr
MEK targeting in N-RAS mutated metastatic melanoma.
2014 Mar 4
Combined PKC and MEK inhibition in uveal melanoma with GNAQ and GNA11 mutations.
2014 Sep 25
Patents

Patents

Sample Use Guides

In Vivo Use Guide
MEK162 administered as a fixed dose of 45 mg (3 x 15 mg tablets) BID, with a glass of water and taken with or without food.
Route of Administration: Oral
In Vitro Use Guide
MCF7 (mutant PIK3CA) breast cancer cells exhibiting sensitivity to PI3K inhibition were seeded in 12-well plates (2 × 10^4). After 24 hours, cells were treated with BEZ235, BKM120, GDC-0941, or MK2206 alone or in combination with MEK162. MEK162 (1 uM) combined with MK-2206 (2 mM) completely reversed the resistance of RSK-expressing MCF7 cells.
Substance Class Chemical
Created
by admin
on Mon Oct 21 23:08:14 UTC 2019
Edited
by admin
on Mon Oct 21 23:08:14 UTC 2019
Record UNII
181R97MR71
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
BINIMETINIB
INN   USAN   WHO-DD  
INN   USAN  
Official Name English
5-((4-BROMO-2-FLUOROPHENYLAMINO)-4-FLUORO-N-(2-HYDROXYETHOXY)-1-METHYL-1H-BENZO (D) IMIDAZOLE-6-CARBOXAMIDE
Systematic Name English
5-((4-BROMO-2-FLUOROPHENYL)AMINO)-4-FLUORO-N-(2-HYDROXYETHOXY)-1-METHYL-1H-BENZIMIDAZOLE-6-CARBOXAMIDE
Systematic Name English
BINIMETINIB [INN]
Common Name English
BINIMETINIB [USAN]
Common Name English
BINIMETINIB [JAN]
Common Name English
MEK162
Code English
ARRY-438162
Code English
MEKTOVI
Brand Name English
NVP-MEK162
Code English
1H-BENZIMIDAZOLE-6-CARBOXAMIDE, 5-((4-BROMO-2-FLUOROPHENYL)AMINO)-4-FLUORO-N-(2-HYDROXYETHOXY)-1-METHYL-
Systematic Name English
ARRY-162
Code English
BINIMETINIB [WHO-DD]
Common Name English
5-(4-BROMO-2-FLUOROPHENYLAMINO)-4-FLUORO-N-(2-HYDROXYETHOXY)-1-METHYL-1H-BENZO(D)IMIDAZOLE-6-CARBOXAMIDE
Systematic Name English
ARRY 438162
Code English
MEK-162
Code English
Classification Tree Code System Code
FDA ORPHAN DRUG 411613
Created by admin on Mon Oct 21 23:08:15 UTC 2019 , Edited by admin on Mon Oct 21 23:08:15 UTC 2019
NCI_THESAURUS C69145
Created by admin on Mon Oct 21 23:08:15 UTC 2019 , Edited by admin on Mon Oct 21 23:08:15 UTC 2019
NCI_THESAURUS C129825
Created by admin on Mon Oct 21 23:08:15 UTC 2019 , Edited by admin on Mon Oct 21 23:08:15 UTC 2019
WHO-ATC L01XE41
Created by admin on Mon Oct 21 23:08:15 UTC 2019 , Edited by admin on Mon Oct 21 23:08:15 UTC 2019
FDA ORPHAN DRUG 411513
Created by admin on Mon Oct 21 23:08:15 UTC 2019 , Edited by admin on Mon Oct 21 23:08:15 UTC 2019
FDA ORPHAN DRUG 440414
Created by admin on Mon Oct 21 23:08:15 UTC 2019 , Edited by admin on Mon Oct 21 23:08:15 UTC 2019
Code System Code Type Description
NCI_THESAURUS
C84865
Created by admin on Mon Oct 21 23:08:15 UTC 2019 , Edited by admin on Mon Oct 21 23:08:15 UTC 2019
PRIMARY
EVMPD
SUB179942
Created by admin on Mon Oct 21 23:08:15 UTC 2019 , Edited by admin on Mon Oct 21 23:08:15 UTC 2019
PRIMARY
INN
9764
Created by admin on Mon Oct 21 23:08:15 UTC 2019 , Edited by admin on Mon Oct 21 23:08:15 UTC 2019
PRIMARY
CAS
606143-89-9
Created by admin on Mon Oct 21 23:08:15 UTC 2019 , Edited by admin on Mon Oct 21 23:08:15 UTC 2019
PRIMARY
PUBCHEM
10288191
Created by admin on Mon Oct 21 23:08:15 UTC 2019 , Edited by admin on Mon Oct 21 23:08:15 UTC 2019
PRIMARY
EPA CompTox
606143-89-9
Created by admin on Mon Oct 21 23:08:15 UTC 2019 , Edited by admin on Mon Oct 21 23:08:15 UTC 2019
PRIMARY
WIKIPEDIA
Binimetinib
Created by admin on Mon Oct 21 23:08:15 UTC 2019 , Edited by admin on Mon Oct 21 23:08:15 UTC 2019
PRIMARY
ChEMBL
CHEMBL3187723
Created by admin on Mon Oct 21 23:08:15 UTC 2019 , Edited by admin on Mon Oct 21 23:08:15 UTC 2019
PRIMARY
Related Record Type Details
METABOLIC ENZYME -> SUBSTRATE
METABOLIC ENZYME -> SUBSTRATE
EXCRETED UNCHANGED
FECAL
METABOLIC ENZYME -> INHIBITOR
MINOR
IC50
METABOLIC ENZYME -> SUBSTRATE
TRANSPORTER -> INHIBITOR
MINOR
IC50
BINDER->LIGAND
TRANSPORTER -> SUBSTRATE
METABOLIC ENZYME -> SUBSTRATE
EXCRETED UNCHANGED
URINE
TRANSPORTER -> SUBSTRATE
TARGET -> INHIBITOR
IC50
TARGET -> INHIBITOR
IC50
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Volume of Distribution PHARMACOKINETIC DOSE

Biological Half-life PHARMACOKINETIC
Tmax PHARMACOKINETIC DOSE