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Binimetinib

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Also known as ARRY 438162ARRY-162ARRY-438162Mek-162MEK162MektoviNVP-MEK162SID174006430

Summary

Binimetinib (CHEMBL3187723) is an approved small-molecule EC 2.7.11.24 (mitogen-activated protein kinase) inhibitor (ATC L01EE03) targeting MAP2K1 and MAP2K2; indicated across 34 conditions including metastatic melanoma and cutaneous melanoma; with CIViC clinical evidence for 16 variant-indication associations (e.g. BRAF V600 in melanoma).

At a glance

  • Status: Approved (max clinical phase 4)
  • Modality: Small molecule
  • ATC class: L01EE03
  • Targets: 2 (MAP2K1, MAP2K2)
  • Indications: 34 conditions
  • Clinical trials: 125
  • Precision-oncology evidence (CIViC): 16 variant–indication associations
  • Chemistry: 441.2 Da · C17H15BrF2N4O3

Identifiers

Drug identity and classification

FieldValue
ChEMBL IDCHEMBL3187723
NameBinimetinib
TypeSmall molecule
Max phase4
FDA approvedyes
PubChem CID10288191
ChEBICHEBI:145371
ATCL01EE03
Molecular formulaC17H15BrF2N4O3
Molecular weight441.2
InChIKeyACWZRVQXLIRSDF-UHFFFAOYSA-N

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

IUPAC name: 6-(4-bromo-2-fluoroanilino)-7-fluoro-N-(2-hydroxyethoxy)-3-methylbenzimidazole-5-carboxamide

ChEBI definition: A member of the class of benzimidazoles that is 1-methyl-1H-benzimidazole which is substituted at positions 4, 5, and 6 by fluorine, (4-bromo-2-fluorophenyl)nitrilo, and N-(2-hydroxyethoxy)aminocarbonyl groups, respectively. It is a MEK1 and MEK2 inhibitor (IC50= 12 nM). Approved by the FDA for the treatment of patients with unresectable or metastatic melanoma with a BRAF V600E or V600K mutation in combination with encorafenib.

Pharmacological roles (ChEBI): EC 2.7.11.24 (mitogen-activated protein kinase) inhibitor, antineoplastic agent, apoptosis inducer.

Also known as: ARRY 438162, ARRY-162, ARRY-438162, Binimetinib, Mek-162, MEK-162, MEK162, Mektovi, NVP-MEK162, SID174006430, BINIMETINIB, binimetinib

Patent coverage: 2,815 distinct patent families (7,280 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 7,035 (97%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

GeneTargetActionpAffinityCancer dependencyUniProt
MAP2K1mitogen-activated protein kinase kinase 1Negative7.924.7%Q02750
MAP2K2mitogen-activated protein kinase kinase 2Negative7.923.1%P36507

Broader ChEMBL bioactivity targets: 5 (assay-derived). Sample: Dual specificity mitogen-activated protein kinase kinase; MEK1/2, Dual specificity mitogen-activated protein kinase kinase 2, Dual specificity mitogen-activated protein kinase kinase 1, Ribosyldihydronicotinamide dehydrogenase [quinone], Bile salt export pump.

Bioactivity

ChEMBL activities: 5 potent at pChembl ≥ 5 of 7 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

TargetpChemblTypeValueUnitActivity ID
MAP2K17.92IC5012nMCHEMBL_ACT_25564479
MAP2K27.92IC5012nMCHEMBL_ACT_26186131
MAP2K27.92IC5012nMCHEMBL_ACT_29048795
MAP2K27.44Kd36nMCHEMBL_ACT_17910583
MAP2K17.35Kd45nMCHEMBL_ACT_17910464

Target pathways

Aggregated over 2 target gene(s): MAP2K1, MAP2K2.

Top Reactome pathways

62 total, by targets touching each:

PathwayTargetsGenes
RAF-independent MAPK1/3 activation2MAP2K1, MAP2K2
Developmental Biology2MAP2K1, MAP2K2
Signal Transduction2MAP2K1, MAP2K2
Disease2MAP2K1, MAP2K2
Signaling by NTRKs2MAP2K1, MAP2K2
Prolonged ERK activation events2MAP2K1, MAP2K2
Frs2-mediated activation2MAP2K1, MAP2K2
Signaling by NTRK1 (TRKA)2MAP2K1, MAP2K2
Signalling to ERKs2MAP2K1, MAP2K2
L1CAM interactions2MAP2K1, MAP2K2
Axon guidance2MAP2K1, MAP2K2
Signal transduction by L12MAP2K1, MAP2K2
Uptake and function of anthrax toxins2MAP2K1, MAP2K2
Uptake and actions of bacterial toxins2MAP2K1, MAP2K2
Diseases of signal transduction by growth factor receptors and second messengers2MAP2K1, MAP2K2
Infectious disease2MAP2K1, MAP2K2
RAF activation2MAP2K1, MAP2K2
RAF/MAP kinase cascade2MAP2K1, MAP2K2
MAP2K and MAPK activation2MAP2K1, MAP2K2
Negative feedback regulation of MAPK pathway2MAP2K1, MAP2K2
Negative regulation of MAPK pathway2MAP2K1, MAP2K2
MAPK family signaling cascades2MAP2K1, MAP2K2
MAPK1/MAPK3 signaling2MAP2K1, MAP2K2
Signaling by moderate kinase activity BRAF mutants2MAP2K1, MAP2K2
Signaling by high-kinase activity BRAF mutants2MAP2K1, MAP2K2
Signaling by RAS mutants2MAP2K1, MAP2K2
Signaling by BRAF and RAF1 fusions2MAP2K1, MAP2K2
Paradoxical activation of RAF signaling by kinase inactive BRAF2MAP2K1, MAP2K2
Oncogenic MAPK signaling2MAP2K1, MAP2K2
Signaling by Receptor Tyrosine Kinases2MAP2K1, MAP2K2

Dominant GO biological processes

GO termTargets
MAPK cascade2
heart development2
positive regulation of gene expression2
Schwann cell development2
thyroid gland development2
regulation of stress-activated MAPK cascade2
ERBB2-ERBB3 signaling pathway2
myelination2
positive regulation of DNA-templated transcription2
insulin-like growth factor receptor signaling pathway2
thymus development2
regulation of axon regeneration2
positive regulation of axonogenesis2
face development2
trachea formation2

Indications & clinical

Indications

34 indications (5 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

IndicationTrial phaseMONDOEFO
metastatic melanoma4MONDO:0005191EFO:0002617
cutaneous melanoma4MONDO:0005012EFO:0000389
neoplasm4MONDO:0005070EFO:0000616
melanoma4MONDO:0005105EFO:0000756
peritoneal neoplasm3MONDO:0006901MONDO:0002087
fallopian tube neoplasm3MONDO:0021092MONDO:0002158
ovarian cancer3MONDO:0008170MONDO:0008170
ovarian carcinoma3MONDO:0005140EFO:0001075
biliary tract neoplasm3MONDO:0005304EFO:0003891
rheumatoid arthritis2MONDO:0008383EFO:0000685
plasma cell myeloma2MONDO:0009693EFO:0001378
non-small cell lung carcinoma2MONDO:0005233EFO:0003060
colorectal carcinoma2MONDO:0024331EFO:1001951
breast carcinoma2MONDO:0004989EFO:0000305
thyroid gland carcinoma2MONDO:0015075EFO:0002892
exocrine pancreatic carcinoma2MONDO:0005192EFO:0002618
hairy cell leukemia2MONDO:0018935EFO:1000956
breast neoplasm2MONDO:0021100MONDO:0007254
triple-negative breast carcinoma2MONDO:0005494EFO:0005537
hilar cholangiocarcinoma2MONDO:0003345EFO:1001959
uveal melanoma2MONDO:0006486EFO:1000616
colorectal neoplasm2MONDO:0005335MONDO:0005575
liver disorder1MONDO:0005154EFO:0001421
leukemia1MONDO:0005059EFO:0000565
rectal cancer1MONDO:0006519EFO:1000657
lung neoplasm1MONDO:0021117MONDO:0008903
colonic neoplasm1MONDO:0005401MONDO:0021063
brain neoplasm1MONDO:0021211EFO:0003833
gastrointestinal stromal tumor1MONDO:0011719MONDO:0011719
glioma1MONDO:0021042MONDO:0021637
skin carcinoma0MONDO:0002656EFO:0009259

3 further indication records had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 125.

Phase distribution

PhaseTrials
PHASE251
PHASE135
PHASE1/PHASE222
PHASE38
Not specified5
EARLY_PHASE13
PHASE41

Top trials by phase / activity

NCTPhaseStatusTitle
NCT05203172PHASE4RECRUITINGThe FLOTILLA Study: Providing Continued Access to The Study Medicines Encorafenib and Binimetinib for Participants in Prior Clinical Trials
NCT03803553PHASE3RECRUITINGIdentification and Treatment Of Micrometastatic Disease in Stage III Colon Cancer
NCT04657991PHASE3ACTIVE_NOT_RECRUITINGA Clinical Trial of Three Study Medicines (Encorafenib, Binimetinib, and Pembrolizumab) in Patients With Advanced or Metastatic Melanoma
NCT05270044PHASE3ACTIVE_NOT_RECRUITINGAdjuvant Encorafenib and Binimetinib in High-risk Stage II Melanoma With a BRAF Mutation.
NCT05615818PHASE3RECRUITINGPersonalized Medicine for Advanced Biliary Cancer Patients
NCT01763164PHASE3COMPLETEDStudy Comparing the Efficacy of MEK162 Versus Dacarbazine in Unresectable or Metastatic NRAS Mutation-positive Melanoma
NCT01849874PHASE3TERMINATEDA Study of MEK162 vs. Physician’s Choice Chemotherapy in Patients With Low-grade Serous Ovarian, Fallopian Tube or Peritoneal Cancer
NCT01909453PHASE3COMPLETEDStudy Comparing Combination of LGX818 Plus MEK162 Versus Vemurafenib and LGX818 Monotherapy in BRAF Mutant Melanoma
NCT02928224PHASE3COMPLETEDStudy of Encorafenib + Cetuximab Plus or Minus Binimetinib vs. Irinotecan/Cetuximab or Infusional 5-Fluorouracil (5-FU)/Folinic Acid (FA)/Irinotecan (FOLFIRI)/Cetuximab With a Safety Lead-in of Encorafenib + Binimetinib + Cetuximab in Patients With BRAF V600E-mutant Metastatic Colorectal Cancer
NCT01991379PHASE1/PHASE2ACTIVE_NOT_RECRUITINGMEK162 in Combination With Imatinib Mesylate in Patients With Untreated Advanced Gastrointestinal Stromal Tumor (GIST)
NCT02465060PHASE2ACTIVE_NOT_RECRUITINGTargeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma (The MATCH Screening Trial)
NCT02910700PHASE2ACTIVE_NOT_RECRUITINGNivolumab With Trametinib and Dabrafenib, or Encorafenib and Binimetinib in Treating Patients With BRAF Mutated Metastatic or Unresectable Stage III-IV Melanoma
NCT03235245PHASE2ACTIVE_NOT_RECRUITINGImmunotherapy With Ipilimumab and Nivolumab Preceded or Not by a Targeted Therapy With Encorafenib and Binimetinib
NCT03563729PHASE2RECRUITINGMelanoma Metastasized to the Brain and Steroids
NCT03839342PHASE2ACTIVE_NOT_RECRUITINGBinimetinib and Encorafenib for the Treatment of Advanced Solid Tumors With Non-V600E BRAF Mutations
NCT03947385PHASE1/PHASE2RECRUITINGStudy of IDE196 in Patients With Solid Tumors Harboring GNAQ/11 Mutations or PRKC Fusions
NCT03971409PHASE2ACTIVE_NOT_RECRUITINGAvelumab With Binimetinib, Sacituzumab Govitecan, or Liposomal Doxorubicin in Treating Stage IV or Unresectable, Recurrent Triple Negative Breast Cancer
NCT04061980PHASE2ACTIVE_NOT_RECRUITINGEncorafenib and Binimetinib With or Without Nivolumab in Treating Patients With Metastatic Radioiodine Refractory BRAF V600 Mutant Thyroid Cancer
NCT04074096PHASE2ACTIVE_NOT_RECRUITINGBinimetinib Encorafenib Pembrolizumab +/- Stereotactic Radiosurgery in BRAFV600 Melanoma With Brain Metastasis
NCT04322383PHASE2RECRUITINGBinimetinib for People With Relapsed/Refractory BRAF Wild Type Hairy Cell Leukemia and Variant
NCT04324112PHASE2RECRUITINGEncorafenib Plus Binimetinib for People With BRAF V600 Mutated Relapsed/Refractory HCL
NCT04439344PHASE2ACTIVE_NOT_RECRUITINGTesting Binimetinib as a Potential Targeted Treatment in Cancers With NRAS Genetic Changes (MATCH-Subprotocol Z1A)
NCT04511013PHASE2RECRUITINGA Study to Compare the Administration of Encorafenib + Binimetinib + Nivolumab Versus Ipilimumab + Nivolumab in BRAF-V600 Mutant Melanoma With Brain Metastases
NCT04526782PHASE2ACTIVE_NOT_RECRUITINGENCOrafenib With Binimetinib in bRAF NSCLC
NCT04598009PHASE2RECRUITINGBinimetinib and Imatinib for Unresectable Stage III-IV KIT-Mutant Melanoma
NCT05026983PHASE2RECRUITINGBinimetinib and Encorafenib for the Treatment of Metastatic Melanoma and Central Nervous System Metastases
NCT05170334PHASE2ACTIVE_NOT_RECRUITINGBinimetinib Plus Belinostat for Subjects With Metastatic Uveal Melanoma
NCT05195632PHASE2ACTIVE_NOT_RECRUITINGPhase II Study Investigating the Combination of Encorafenib and Binimetinib in BRAF V600E Mutated Chinese Patients With Metastatic Non-Small Cell Lung Cancer
NCT05554367PHASE2ACTIVE_NOT_RECRUITINGPalbociclib and Binimetinib in RAS-Mutant Cancers, A ComboMATCH Treatment Trial
NCT05564377PHASE2RECRUITINGTargeted Therapy Directed by Genetic Testing in Treating Patients With Locally Advanced or Advanced Solid Tumors, The ComboMATCH Screening Trial
NCT05564403PHASE2ACTIVE_NOT_RECRUITINGStudy of Chemotherapy, With or Without Binimetinib in Advanced Biliary Tract Cancers in 2nd Line Setting (A ComboMATCH Treatment Trial)
NCT06159478PHASE2RECRUITINGBinimetinib in Patients With BRAF Fusion-positive Low-grade Glioma or Pancreatic Cancer (Perfume)
NCT06887088PHASE2RECRUITINGEncorafenib and biNimetinib Followed by CEmiplimab and FiAnLimab in Patients With BRAF Mutant melanOma and Symptomatic Brain Metastases
NCT00650767PHASE2COMPLETEDA Study of ARRY-438162 in Patients With Rheumatoid Arthritis
NCT01320085PHASE2COMPLETEDA Phase II Study of Single Agent MEK162 in Patients With Advanced Melanoma
NCT01543698PHASE1/PHASE2COMPLETEDA Phase Ib/II Study of LGX818 in Combination With MEK162 in Adult Patients With BRAF Dependent Advanced Solid Tumors
NCT01556568PHASE2WITHDRAWNSafety, Tolerability, Pharmacokinetics and Pharmacodynamics of MEK162 in Noonan Syndrome Hypertrophic Cardiomyopathy
NCT01562899PHASE1/PHASE2TERMINATEDA Study of MEK162 and AMG 479 in Patients With Selected Solid Tumors
NCT01781572PHASE1/PHASE2COMPLETEDA Phase Ib/II Study of LEE011 in Combination With MEK162 in Patients With NRAS Mutant Melanoma
NCT01801358PHASE1/PHASE2TERMINATEDA Phase Ib/II Study of AEB071 and MEK162 in Adult Patients With Metastatic Uveal Melanoma

Clinical evidence (CIViC)

Variant × indication × effect (16 predictive associations from 17 curated evidence items):

VariantIndicationEffectTherapyLevelCIViC
BRAF V600MelanomaSensitivity/ResponseEncorafenib + BinimetinibCIViC AEID7287
NRAS MutationSkin MelanomaSensitivity/ResponseBinimetinibCIViC BEID1472 +1
BRAF V600EColorectal CancerSensitivity/ResponseEncorafenib + Binimetinib + CetuximabCIViC BEID7260
BRAF V600EColorectal CancerSensitivity/ResponseEncorafenib + Cetuximab + BinimetinibCIViC BEID7612
KRAS MutationOvary Serous AdenocarcinomaSensitivity/ResponseBinimetinibCIViC BEID8773
NRAS MutationSolid TumorSensitivity/ResponseBinimetinibCIViC BEID11674
NRAS MutationSkin MelanomaSensitivity/ResponseRibociclib + BinimetinibCIViC BEID2931
NRAS Q61Skin MelanomaSensitivity/ResponseBinimetinibCIViC BEID1226
KRAS G12DColorectal CancerSensitivity/ResponseBinimetinib + Bevacizumab + HydroxychloroquineCIViC CEID10797
MAP2K1 V211DColorectal CancerResistanceBinimetinib + PanitumumabCIViC CEID7580
HRAS MutationCancerSensitivity/ResponseSelumetinib + Mirdametinib + MTOR Kinase Inhibitor AZD8055 + Everolimus + BinimetinibCIViC DEID700
KRAS MutationColorectal CancerSensitivity/ResponsePalbociclib + BinimetinibCIViC DEID4869
NF1 LossNeuroblastomaSensitivity/ResponseBinimetinibCIViC DEID1956
NRAS AmplificationMelanomaSensitivity/ResponseBinimetinibCIViC DEID6899
NRAS MutationMelanomaSensitivity/ResponseBinimetinibCIViC DEID1509
NRAS Q61KNeuroblastomaSensitivity/ResponseEverolimus + BinimetinibCIViC DEID1002

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline or drug-level clinical/variant annotations in PharmGKB for this molecule.

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

71 molecules share ≥1 primary target. Top 60 by shared-target count:

MoleculeSourceStatusShared targets
COBIMETINIBChEMBL + PubChemPhase 4 (approved)MAP2K1, MAP2K2
FEDRATINIBChEMBL + PubChemPhase 4 (approved)MAP2K1, MAP2K2
RUXOLITINIBChEMBL + PubChemPhase 4 (approved)MAP2K1, MAP2K2
SELUMETINIBChEMBL + PubChemPhase 4 (approved)MAP2K1, MAP2K2
SORAFENIBChEMBL + PubChemPhase 4 (approved)MAP2K1, MAP2K2
TRAMETINIBChEMBL + PubChemPhase 4 (approved)MAP2K1, MAP2K2
VANDETANIBChEMBL + PubChemPhase 4 (approved)MAP2K1, MAP2K2
VEMURAFENIBChEMBL + PubChemPhase 4 (approved)MAP2K1, MAP2K2
AXITINIBChEMBLPhase 4 (approved)MAP2K1, MAP2K2
BOSUTINIBChEMBLPhase 4 (approved)MAP2K1, MAP2K2
DASATINIBChEMBLPhase 4 (approved)MAP2K1, MAP2K2
GILTERITINIBChEMBLPhase 4 (approved)MAP2K1, MAP2K2
NERATINIBChEMBLPhase 4 (approved)MAP2K1, MAP2K2
NINTEDANIBChEMBLPhase 4 (approved)MAP2K1, MAP2K2
SUNITINIBChEMBLPhase 4 (approved)MAP2K1, MAP2K2
AVUTOMETINIBChEMBLPhase 3MAP2K1, MAP2K2
CANERTINIBChEMBLPhase 3MAP2K1, MAP2K2
DOVITINIBChEMBLPhase 3MAP2K1, MAP2K2
LESTAURTINIBChEMBLPhase 3MAP2K1, MAP2K2
LINSITINIBChEMBLPhase 3MAP2K1, MAP2K2
ORANTINIBChEMBLPhase 3MAP2K1, MAP2K2
SARACATINIBChEMBLPhase 3MAP2K1, MAP2K2
CENISERTIBChEMBLPhase 2MAP2K1, MAP2K2
CEP-32496ChEMBLPhase 2MAP2K1, MAP2K2
CI-1040ChEMBLPhase 2MAP2K1, MAP2K2
DEFOSBARASERTIBChEMBLPhase 2MAP2K1, MAP2K2
FORETINIBChEMBLPhase 2MAP2K1, MAP2K2
ILORASERTIBChEMBLPhase 2MAP2K1, MAP2K2
MIRDAMETINIBChEMBLPhase 2MAP2K1, MAP2K2
PELITINIBChEMBLPhase 2MAP2K1, MAP2K2
PIMASERTIBChEMBLPhase 2MAP2K1, MAP2K2
R-406ChEMBLPhase 2MAP2K1, MAP2K2
REFAMETINIBChEMBLPhase 2MAP2K1, MAP2K2
SU-014813ChEMBLPhase 2MAP2K1, MAP2K2
TAK-733ChEMBLPhase 2MAP2K1, MAP2K2
TOZASERTIBChEMBLPhase 2MAP2K1, MAP2K2
AfatinibPubChemApprovedMAP2K1, MAP2K2
CrizotinibPubChemApprovedMAP2K1, MAP2K2
dacomitinibPubChemApprovedMAP2K1, MAP2K2
FostamatinibPubChemApprovedMAP2K1, MAP2K2
GefitinibPubChemApprovedMAP2K1, MAP2K2
IdelalisibPubChemApprovedMAP2K1, MAP2K2
PazopanibPubChemApprovedMAP2K1, MAP2K2
regorafenibPubChemApprovedMAP2K1, MAP2K2
TOFACITINIBChEMBLPhase 4 (approved)MAP2K1
CEDIRANIBChEMBLPhase 3MAP2K2
LINIFANIBChEMBLPhase 3MAP2K2
BIIB-091ChEMBLPhase 2MAP2K2
E-6201ChEMBLPhase 2MAP2K1
SCH-900776ChEMBLPhase 2MAP2K2
SOTRASTAURINChEMBLPhase 2MAP2K1
TOLONIUM CHLORIDEChEMBLPhase 2MAP2K1
ZAPNOMETINIBChEMBLPhase 2MAP2K1
BaricitinibPubChemApprovedMAP2K2
CabozantinibPubChemApprovedMAP2K2
CapivasertibPubChemApprovedMAP2K2
CapmatinibPubChemApprovedMAP2K2
DabrafenibPubChemApprovedMAP2K2
EntrectinibPubChemApprovedMAP2K2
ErlotinibPubChemApprovedMAP2K2

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.2
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Sources 30

This page pulls from 30 datasets indexed by BioBTree:

chebichembl_activitychembl_moleculechembl_targetcivic_evidenceclingen_dosageclinical_trialsdepmapefoensemblentrezgogoparentgtopdbgtopdb_interactiongtopdb_ligandhgncmeshmondomsigdbpatent_compoundpharmgkbpharmgkb_guidelinepubchempubchem_activityreactomereactomeparentrefseqtranscriptuniprot