DGIdb - MAP2K1 Gene Record

MAP2K1 5604 Druggable GenomeClinically ActionableDrug Resistance

Alternate Names:

5604
MITOGEN-ACTIVATED PROTEIN KINASE KINASE 1
MAP2K1
CFC3
MAPKK1
MEK1
MKK1
PRKMK1
176872
6840
ENSG00000169032
OTTHUMG00000133196
Dual specificity mitogen-activated protein kinase kinase 1
ERK activator kinase 1
MAPK/ERK kinase 1
MAP kinase kinase 1
MAPKK 1
MEK 1
Q02750
2062
NM_002755
NP_002746
31
MP2K1_HUMAN
DUAL SPECIFICITY MITOGEN-ACTIVATED PROTEIN KINASE KINASE 1 (EC 2.7.1.-) (MAP KINASE KINASE 1) (MAPKK 1) (ERK ACTIVATOR KINASE 1) (MAPK/ERK KINASE 1) (MEK1). [SOURCE:UNIPROT/SWISSPROT;ACC:Q02750]
MEK
T35940
MEL

Gene Info:

GuideToPharmacology Gene Category Name	STE7 family
GuideToPharmacology Gene Category ID	623
Interpro Name	Serine/threonine- / dual-specificity protein kinase, catalytic domain
Interpro Acc	IPR002290
Human Readable Name	DRUGGABLE GENOME
Uniprot Status	Swiss-Prot
Interpro Type	Domain
Interpro Short Name	Ser/Thr_dual-sp_kinase_dom
Human Readable Name	KINASE
Uniprot Evidence	1: Evidence at protein level
CancerCommons Reported Gene Name	MEK
Target Class	Enzymes
Target Subclass	EC:2.7.12.2
Gene Biotype	PROTEIN_CODING

(24 More Sources)

Gene Categories: Category Details

KINASE
SERINE THREONINE KINASE
TYROSINE KINASE
DRUG RESISTANCE
NUCLEAR HORMONE RECEPTOR
DRUGGABLE GENOME
CLINICALLY ACTIONABLE
ENZYME

Publications:

Grisham et al., 2015, Extreme Outlier Analysis Identifies Occult Mitogen-Activated Protein Kinase Pathway Mutations in Patients With Low-Grade Serous Ovarian Cancer., J. Clin. Oncol.
Emery et al., 2009, MEK1 mutations confer resistance to MEK and B-RAF inhibition., Proc. Natl. Acad. Sci. U.S.A.
Marks et al., 2008, Novel MEK1 mutation identified by mutational analysis of epidermal growth factor receptor signaling pathway genes in lung adenocarcinoma., Cancer Res.
Crystal et al., 2014, Patient-derived models of acquired resistance can identify effective drug combinations for cancer., Science
Oddo et al., 2016, Molecular Landscape of Acquired Resistance to Targeted Therapy Combinations in BRAF-Mutant Colorectal Cancer., Cancer Res.
Nikolaev et al., 2011, Exome sequencing identifies recurrent somatic MAP2K1 and MAP2K2 mutations in melanoma., Nat. Genet.
Gannon et al., 2016, Identification of an "Exceptional Responder" Cell Line to MEK1 Inhibition: Clinical Implications for MEK-Targeted Therapy., Mol. Cancer Res.
Choi et al., 2012, Oncogenic MAP2K1 mutations in human epithelial tumors., Carcinogenesis
Narita et al., 2014, Novel ATP-competitive MEK inhibitor E6201 is effective against vemurafenib-resistant melanoma harboring the MEK1-C121S mutation in a preclinical model., Mol. Cancer Ther.
Catalanotti F et al., 2013, Phase II trial of MEK inhibitor selumetinib (AZD6244, ARRY-142886) in patients with BRAFV600E/K-mutated melanoma., Clin Cancer Res
Yeh et al., 2007, Biological characterization of ARRY-142886 (AZD6244), a potent, highly selective mitogen-activated protein kinase kinase 1/2 inhibitor., Clin. Cancer Res.
Dombi et al., 2016, Activity of Selumetinib in Neurofibromatosis Type 1-Related Plexiform Neurofibromas., N. Engl. J. Med.
Davies et al., 2007, AZD6244 (ARRY-142886), a potent inhibitor of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase 1/2 kinases: mechanism of action in vivo, pharmacokinetic/pharmacodynamic relationship, and potential for combination in preclinical models., Mol. Cancer Ther.
Diamond et al., 2016, Diverse and Targetable Kinase Alterations Drive Histiocytic Neoplasms., Cancer Discov
Singh et al., 2015, Targeted inhibition of MEK1 by cobimetinib leads to differentiation and apoptosis in neuroblastoma cells., J. Exp. Clin. Cancer Res.
MacConaill et al., 2014, Prospective enterprise-level molecular genotyping of a cohort of cancer patients., J Mol Diagn
Bottorff et al., 1995, RAS signalling is abnormal in a c-raf1 MEK1 double mutant., Mol. Cell. Biol.
Trunzer et al., 2013, Pharmacodynamic effects and mechanisms of resistance to vemurafenib in patients with metastatic melanoma., J. Clin. Oncol.
Wagle et al., 2011, Dissecting therapeutic resistance to RAF inhibition in melanoma by tumor genomic profiling., J. Clin. Oncol.
Greger et al., 2012, Combinations of BRAF, MEK, and PI3K/mTOR inhibitors overcome acquired resistance to the BRAF inhibitor GSK2118436 dabrafenib, mediated by NRAS or MEK mutations., Mol. Cancer Ther.
Van Allen et al., 2014, The genetic landscape of clinical resistance to RAF inhibition in metastatic melanoma., Cancer Discov
Salama et al., 2013, Trametinib (GSK1120212) in the treatment of melanoma., Expert Opin Pharmacother
Russo et al., 2016, Tumor Heterogeneity and Lesion-Specific Response to Targeted Therapy in Colorectal Cancer., Cancer Discov
Carlino et al., 2015, Preexisting MEK1P124 mutations diminish response to BRAF inhibitors in metastatic melanoma patients., Clin. Cancer Res.
Wagle et al., 2014, MAP kinase pathway alterations in BRAF-mutant melanoma patients with acquired resistance to combined RAF/MEK inhibition., Cancer Discov
Brammeld et al., 2017, Genome-wide chemical mutagenesis screens allow unbiased saturation of the cancer genome and identification of drug resistance mutations., Genome Res.
Ahronian et al., 2015, Clinical Acquired Resistance to RAF Inhibitor Combinations in BRAF-Mutant Colorectal Cancer through MAPK Pathway Alterations., Cancer Discov
Nelson DS et al., 2015, MAP2K1 and MAP3K1 mutations in Langerhans cell histiocytosis., Genes Chromosomes Cancer
Brown NA et al., 2014, High prevalence of somatic MAP2K1 mutations in BRAF V600E-negative Langerhans cell histiocytosis., Blood
Delaney et al., 2002, Identification of a novel mitogen-activated protein kinase kinase activation domain recognized by the inhibitor PD 184352., Mol. Cell. Biol.
Gao Y et al., 2019, V211D Mutation in MEK1 Causes Resistance to MEK Inhibitors in Colon Cancer., Cancer Discov
Van Dort ME et al., 2015, Dual inhibition of allosteric mitogen-activated protein kinase (MEK) and phosphatidylinositol 3-kinase (PI3K) oncogenic targets with a bifunctional inhibitor., Bioorg Med Chem
Daouti S et al., 2010, Preclinical in vivo evaluation of efficacy, pharmacokinetics, and pharmacodynamics of a novel MEK1/2 kinase inhibitor RO5068760 in multiple tumor models., Mol Cancer Ther
Herrero et al., 2015, Small Molecule Inhibition of ERK Dimerization Prevents Tumorigenesis by RAS-ERK Pathway Oncogenes., Cancer Cell
Vasbinder MM et al., 2013, Discovery and optimization of a novel series of potent mutant B-Raf(V600E) selective kinase inhibitors., J Med Chem
Berman et al., 2000, The Protein Data Bank., Nucleic Acids Res.
Rizos et al., 2014, BRAF inhibitor resistance mechanisms in metastatic melanoma: spectrum and clinical impact., Clin. Cancer Res.

RG-7304 MAP2K1

Interaction Score: 1.91

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Dual specificity mitogen-activated protein kinase kinase 1 inhibitor

Direct Interaction yes

PMIDs:
25766633

Sources:
DTC ChemblInteractions
AZD-8330 MAP2K1

Interaction Score: 1.28

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Trial Name AZD-8330

Novel drug target Novel Target

Mechanism of Interaction Dual specificity mitogen-activated protein kinase kinase 1 inhibitor

PMIDs:
None found

Sources:
TdgClinicalTrial ChemblInteractions
MEKINIST MAP2K1

Interaction Score: 1.28

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Reported Cancer Type Melanoma

PMIDs:
None found

Sources:
CancerCommons
CHEMBL1956073 MAP2K1

Interaction Score: 1.28

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
20053779

Sources:
DTC
PIMASERTIB HYDROCHLORIDE MAP2K1

Interaction Score: 1.28

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Reported Cancer Type Melanoma

PMIDs:
None found

Sources:
CancerCommons
REFAMETINIB MAP2K1

Interaction Score: 1.09

Interaction Types & Directionality:

allosteric modulator

inhibitor (inhibitory)

Interaction Info:

Specific Action of the Ligand Negative

Endogenous Drug? False

Direct Interaction? True

PMIDs:
26582713

Sources:
MyCancerGenome JAX-CKB ChemblInteractions GuideToPharmacology CancerCommons
COBIMETINIB MAP2K1

Interaction Score: 1.09

Interaction Types & Directionality:

allosteric modulator

inhibitor (inhibitory)

Interaction Info:

Direct Interaction yes

Mechanism of Interaction Dual specificity mitogen-activated protein kinase kinase 1 inhibitor

Novel drug target Novel Target

PMIDs:
26566875 26384788

Sources:
TALC MyCancerGenome TdgClinicalTrial ClearityFoundationClinicalTrial JAX-CKB ChemblInteractions GuideToPharmacology CancerCommons MyCancerGenomeClinicalTrial OncoKB
PD-0325901 MAP2K1

Interaction Score: 1.04

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Indication/Tumor Type melanoma

Response Type resistant

Approval Status Preclinical

PMIDs:
26582713 26267534 25766633 23398453 10592235

Sources:
DTC MyCancerGenome JAX-CKB ChemblInteractions

RG-7420 MAP2K1

Interaction Score: 0.96

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Dual specificity mitogen-activated protein kinase kinase 1 inhibitor

Direct Interaction yes

Details of the Assay for Interaction Measured in a fluorescence anisotropy assay using recombinant MEK1. Ki approximated from the graph in supplementary figure 1b.

PMIDs:
None found

Sources:
MyCancerGenome ChemblInteractions GuideToPharmacology

SELUMETINIB MAP2K1

Interaction Score: 0.87

Interaction Types & Directionality:

allosteric modulator

inhibitor (inhibitory)

Interaction Info:

Specific Action of the Ligand Negative

Endogenous Drug? False

Direct Interaction? True

PMIDs:
26324360 19915144 18632602 25394791 27312529 22197931 26582713 22327936 24448821 23444215 17332304 28029918 17699718

Sources:
TALC MyCancerGenome ClearityFoundationClinicalTrial JAX-CKB ChemblInteractions COSMIC CIViC GuideToPharmacology CancerCommons MyCancerGenomeClinicalTrial TTD
TAK-733 MAP2K1

Interaction Score: 0.8

Interaction Types & Directionality:

allosteric modulator

inhibitor (inhibitory)

Interaction Info:

Direct Interaction yes

Mechanism of Interaction Dual specificity mitogen-activated protein kinase kinase 1 inhibitor

Reported Cancer Type Melanoma

PMIDs:
None found

Sources:
MyCancerGenome ClearityFoundationClinicalTrial ChemblInteractions GuideToPharmacology CancerCommons
E-6201 MAP2K1

Interaction Score: 0.73

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Evidence Type Actionable

Approval Status Preclinical

Response Type sensitive

PMIDs:
24448821

Sources:
JAX-CKB ChemblInteractions GuideToPharmacology
TRAMETINIB MAP2K1

Interaction Score: 0.67

Interaction Types & Directionality:

antagonist (inhibitory)

inhibitor (inhibitory)

Interaction Info:

Trial Name GSK1120212

Novel drug target Novel Target

Notes

PMIDs:
23432625 26566875 26644315 25370473 22389471 26582713 24265154 28179366 24265153 27312529 25673644 25899310 24982505

Sources:
TALC MyCancerGenome TdgClinicalTrial ClearityFoundationClinicalTrial JAX-CKB CGI CIViC GuideToPharmacology MyCancerGenomeClinicalTrial OncoKB
AS-703988 MAP2K1

Interaction Score: 0.64

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Dual specificity mitogen-activated protein kinase kinase 1 inhibitor

Direct Interaction yes

PMIDs:
None found

Sources:
ChemblInteractions
COBIMETINIB FUMARATE MAP2K1

Interaction Score: 0.64

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Dual specificity mitogen-activated protein kinase kinase 1 inhibitor

Direct Interaction yes

PMIDs:
None found

Sources:
ChemblInteractions
RG-7167 MAP2K1

Interaction Score: 0.64

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Dual specificity mitogen-activated protein kinase kinase; MEK1/2 inhibitor

Direct Interaction yes

PMIDs:
None found

Sources:
ChemblInteractions
DEL-22379 MAP2K1

Interaction Score: 0.64

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type melanoma

Response Type sensitive

Approval Status Preclinical - Cell culture

PMIDs:
26267534

Sources:
JAX-CKB
TRAMETINIB DIMETHYL SULFOXIDE MAP2K1

Interaction Score: 0.64

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Dual specificity mitogen-activated protein kinase kinase 1 inhibitor

Direct Interaction yes

PMIDs:
None found

Sources:
ChemblInteractions
VEMURAFENIB MAP2K1

Interaction Score: 0.64

Interaction Types & Directionality:

n/a

Interaction Info:

Clinical Status case report

Pathway activation

Variant Effect gain-of-function

PMIDs:
22197931 19915144 25157968 18632602 7651428 23569304 21383288 22389471 24448821 24265153 27312529

Sources:
JAX-CKB CGI DoCM CIViC
DABRAFENIB MAP2K1

Interaction Score: 0.6

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Dabrafenib + SCH772984

Indication/Tumor Type colorectal cancer

Response Type sensitive

PMIDs:
24463458 25370473 22389471 24265154 24265153 27312529 25673644

Sources:
JAX-CKB CIViC
BINIMETINIB MAP2K1

Interaction Score: 0.57

Interaction Types & Directionality:

allosteric modulator

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Dual specificity mitogen-activated protein kinase kinase 1 inhibitor

Direct Interaction yes

Specific Action of the Ligand Negative

PMIDs:
31227518

Sources:
MyCancerGenome TdgClinicalTrial ClearityFoundationClinicalTrial ChemblInteractions CIViC GuideToPharmacology MyCancerGenomeClinicalTrial
PIMASERTIB MAP2K1

Interaction Score: 0.57

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Notes

Mechanism of Interaction Dual specificity mitogen-activated protein kinase kinase 1 inhibitor

Direct Interaction yes

PMIDs:
None found

Sources:
TALC MyCancerGenome ClearityFoundationClinicalTrial ChemblInteractions
ARRY-300 MAP2K1

Interaction Score: 0.43

Interaction Types & Directionality:

n/a

Interaction Info:

Trial Name ARRY-300

Novel drug target Novel Target

PMIDs:
None found

Sources:
TdgClinicalTrial
PLX-4720 MAP2K1

Interaction Score: 0.38

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type melanoma

Response Type resistant

Approval Status Preclinical

PMIDs:
19915144 21383288

Sources:
JAX-CKB
RO-4987655 MAP2K1

Interaction Score: 0.36

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Dual specificity mitogen-activated protein kinase kinase 1 inhibitor

Direct Interaction yes

Reported Cancer Type Melanoma

PMIDs:
None found

Sources:
ChemblInteractions CancerCommons
WX-554 MAP2K1

Interaction Score: 0.36

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Trial Name WX-554

Novel drug target Novel Target

Mechanism of Interaction Dual specificity mitogen-activated protein kinase kinase 1 inhibitor

PMIDs:
None found

Sources:
TdgClinicalTrial ChemblInteractions
CI-1040 MAP2K1

Interaction Score: 0.33

Interaction Types & Directionality:

allosteric modulator

inhibitor (inhibitory)

Interaction Info:

Indication/Tumor Type melanoma

Response Type resistant

Approval Status Preclinical - Cell culture

PMIDs:
12370306 19915144

Sources:
MyCancerGenome JAX-CKB ChemblInteractions GuideToPharmacology
ENCORAFENIB MAP2K1

Interaction Score: 0.32

Interaction Types & Directionality:

n/a

Interaction Info:

Response Type resistant

Evidence Type Actionable

Approval Status Preclinical - Cell culture

PMIDs:
27312529

Sources:
JAX-CKB
BALAMAPIMOD MAP2K1

Interaction Score: 0.32

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Dual specificity mitogen-activated protein kinase kinase 1 inhibitor

Direct Interaction yes

PMIDs:
None found

Sources:
ChemblInteractions
PANITUMUMAB MAP2K1

Interaction Score: 0.3

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Panitumumab + Trametinib

Indication/Tumor Type colorectal cancer

Response Type sensitive

PMIDs:
26644315 31227518

Sources:
JAX-CKB CGI CIViC
CERITINIB MAP2K1

Interaction Score: 0.21

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Ceritinib + Selumetinib

Indication/Tumor Type non-small cell lung carcinoma

Response Type sensitive

PMIDs:
25394791

Sources:
JAX-CKB
CETUXIMAB MAP2K1

Interaction Score: 0.14

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Vemurafenib + Cetuximab

Indication/Tumor Type colorectal cancer

Response Type sensitive

PMIDs:
26644315 28179366 27312529

Sources:
JAX-CKB CIViC
OMIPALISIB MAP2K1

Interaction Score: 0.13

Interaction Types & Directionality:

n/a

Interaction Info:

Response Type conflicting

Response Type no benefit

combination therapy GSK2126458 + Trametinib

PMIDs:
22389471

Sources:
JAX-CKB
ALPELISIB MAP2K1

Interaction Score: 0.08

Interaction Types & Directionality:

n/a

Interaction Info:

Evidence Type Actionable

Approval Status Preclinical - Cell culture

Response Type sensitive

PMIDs:
27312529

Sources:
JAX-CKB
CHEMBL202721 MAP2K1

Interaction Score: 0.08

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
DTC
CHEMBL406845 MAP2K1

Interaction Score: 0.05

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
DTC
CHEMBL546797 MAP2K1

Interaction Score: 0.04

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
DTC
STAUROSPORINE MAP2K1

Interaction Score: 0.03

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
DTC
CHEMBL379975 MAP2K1

Interaction Score: 0.03

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
DTC
JNJ-7706621 MAP2K1

Interaction Score: 0.02

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
DTC
PD-0166285 MAP2K1

Interaction Score: 0.02

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
DTC
VANDETANIB MAP2K1

Interaction Score: 0.02

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
DTC
SOTRASTAURIN MAP2K1

Interaction Score: 0.02

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
DTC
TOZASERTIB MAP2K1

Interaction Score: 0.02

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
DTC
DASATINIB MAP2K1

Interaction Score: 0.02

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
DTC
RG-1530 MAP2K1

Interaction Score: 0.01

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
DTC
DOVITINIB MAP2K1

Interaction Score: 0.01

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
DTC
TAE-684 MAP2K1

Interaction Score: 0.01

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
DTC
ILORASERTIB MAP2K1

Interaction Score: 0.01

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
DTC
CENISERTIB MAP2K1

Interaction Score: 0.01

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
DTC

Ensembl: ENSG00000169032
- Version: 101_38
Alternate Names:

MAP2K1 Ensembl Gene Name

Gene Info:

Gene Biotype PROTEIN_CODING

Publications:
HopkinsGroom: Q02750
- Version: 11-September-2012
Alternate Names:

Q02750 Uniprot Accession

MP2K1_HUMAN Uniprot Id

5604 Entrez Gene Id

Gene Info:

Interpro Name Serine/threonine- / dual-specificity protein kinase, catalytic domain

Interpro Acc IPR002290

Human Readable Name DRUGGABLE GENOME

Gene Categories:

KINASE, DRUGGABLE GENOME

Publications:

RussLampel: ENSG00000169032

Version: 26-July-2011

Alternate Names:

DUAL SPECIFICITY MITOGEN-ACTIVATED PROTEIN KINASE KINASE 1 (EC 2.7.1.-) (MAP KINASE KINASE 1) (MAPKK 1) (ERK ACTIVATOR KINASE 1) (MAPK/ERK KINASE 1) (MEK1). [SOURCE:UNIPROT/SWISSPROT;ACC:Q02750] Description

ENSG00000169032 Ensembl Gene Id

MAP2K1 Display Id

Gene Info:

Human Readable Name DRUGGABLE GENOME

Gene Categories:

DRUGGABLE GENOME

Publications:

CancerCommons: MAP2K1
- Version: 25-July-2013
Alternate Names:

5604 Entrez Gene ID

Gene Info:

CancerCommons Reported Gene Name MEK

Publications:
TdgClinicalTrial: Q02750
- Version: January-2014
Alternate Names:

MAP2K1 Gene Symbol

Gene Info:

Target Class Enzymes

Target Subclass EC:2.7.12.2

Publications:
GuideToPharmacology: 5604
- Version: 29-September-2020
Alternate Names:

6840 HUGO Gene ID

6840 HUGO Gene Symbol

mitogen-activated protein kinase kinase 1 HUGO Gene Name

Gene Info:

GuideToPharmacology Gene Category Name STE7 family

GuideToPharmacology Gene Category ID 623

Gene Categories:

ENZYME

Publications:

JAX-CKB: MAP2K1

Version: 27-September-2017

Alternate Names:

5604 CKB Entrez Id

MAP2K1 CKB Gene Synonym

CFC3 CKB Gene Synonym

Gene Info:

Publications:

Delaney et al., 2002, Identification of a novel mitogen-activated protein kinase kinase activation domain recognized by the inhibitor PD 184352., Mol. Cell. Biol.

Emery et al., 2009, MEK1 mutations confer resistance to MEK and B-RAF inhibition., Proc. Natl. Acad. Sci. U.S.A.

Oddo et al., 2016, Molecular Landscape of Acquired Resistance to Targeted Therapy Combinations in BRAF-Mutant Colorectal Cancer., Cancer Res.

CIViC: MAP2K1

Version: 14-September-2020

Alternate Names:

5604 Entrez Gene ID

31 CIViC Gene ID

Gene Info:

Gene Categories:

DRUG RESISTANCE

Publications:

Van Allen et al., 2014, The genetic landscape of clinical resistance to RAF inhibition in metastatic melanoma., Cancer Discov

Ahronian et al., 2015, Clinical Acquired Resistance to RAF Inhibitor Combinations in BRAF-Mutant Colorectal Cancer through MAPK Pathway Alterations., Cancer Discov

Wagle et al., 2011, Dissecting therapeutic resistance to RAF inhibition in melanoma by tumor genomic profiling., J. Clin. Oncol.

DoCM: MAP2K1

Version: 27-September-2017

Alternate Names:

Gene Info:

Publications:

Nikolaev et al., 2011, Exome sequencing identifies recurrent somatic MAP2K1 and MAP2K2 mutations in melanoma., Nat. Genet.

Bottorff et al., 1995, RAS signalling is abnormal in a c-raf1 MEK1 double mutant., Mol. Cell. Biol.

Marks et al., 2008, Novel MEK1 mutation identified by mutational analysis of epidermal growth factor receptor signaling pathway genes in lung adenocarcinoma., Cancer Res.

DTC: MAP2K1

Version: 02-September-2020

Alternate Names:

Gene Info:

Publications:

Van Dort ME et al., 2015, Dual inhibition of allosteric mitogen-activated protein kinase (MEK) and phosphatidylinositol 3-kinase (PI3K) oncogenic targets with a bifunctional inhibitor., Bioorg Med Chem

Daouti S et al., 2010, Preclinical in vivo evaluation of efficacy, pharmacokinetics, and pharmacodynamics of a novel MEK1/2 kinase inhibitor RO5068760 in multiple tumor models., Mol Cancer Ther

Vasbinder MM et al., 2013, Discovery and optimization of a novel series of potent mutant B-Raf(V600E) selective kinase inhibitors., J Med Chem

HingoraniCasas: ENSG00000169032
- Version: 31-May-2017
Alternate Names:

ENSG00000169032 Gene Symbol

MAP2K1 Ensembl Id

Gene Info:

Gene Categories:

DRUGGABLE GENOME

Publications:
MyCancerGenome: MAP2K1
- Version: 20-Jun-2017
Alternate Names:

5604 Entrez Gene Id

MAP2K1 MyCancerGenome Gene Symbol

MEK MyCancerGenome Reported Gene Name

Gene Info:

Publications:
TALC: MEK1
- Version: 12-May-2016
Alternate Names:

MEK1 Gene Symbol

Gene Info:

Publications:
ChemblInteractions: MEK1
- Version: chembl_23
Alternate Names:

PRKMK1 GENE_SYMBOL

MEK1 GENE_SYMBOL

MAP2K1 GENE_SYMBOL

Gene Info:

Publications:
OncoKB: MAP2K1
- Version: 23-July-2020
Alternate Names:

5604 OncoKB Entrez Id

MKK1 OncoKB Gene Synonym

PRKMK1 OncoKB Gene Synonym

Gene Info:

Publications:
Tempus: MAP2K1
- Version: 11-November-2018
Alternate Names:

MAP2K1 Gene Symbol

Gene Info:

Gene Categories:

CLINICALLY ACTIONABLE

Publications:
dGene: MAP2K1
- Version: 27-Jun-2013
Alternate Names:

5604 Gene ID

MAPKK1 dGene Synonym

MEK1 dGene Synonym

Gene Info:

Gene Categories:

KINASE, SERINE THREONINE KINASE

Publications:
TTD: ERK activator kinase 1
- Version: 2020.06.01
Alternate Names:

MEK1 TTD Gene Abbreviation

T35940 TTD Target ID

Gene Info:

Publications:
GO: MAP2K1
- Version: 01-May-2021
Alternate Names:

MEK1 GO Gene Synonym

PRKMK1 GO Gene Synonym

Gene Info:

Gene Categories:

SERINE THREONINE KINASE, TYROSINE KINASE

Publications:
Pharos: MAP2K1
- Version: 01-May-2021
Alternate Names:

Dual specificity mitogen-activated protein kinase kinase 1 Gene Name

Q02750 UniProt ID

Gene Info:

Gene Categories:

KINASE, NUCLEAR HORMONE RECEPTOR

Publications:
ClearityFoundationClinicalTrial: MEK1
- Version: 15-June-2013
Alternate Names:

Gene Info:

Publications:
MskImpact: MAP2K1
- Version: May-2015
Alternate Names:

Gene Info:

Gene Categories:

CLINICALLY ACTIONABLE

Publications:
CGI: MAP2K1
- Version: 27-September-2017
Alternate Names:

Gene Info:

Publications:
MyCancerGenomeClinicalTrial: MAP2K1
- Version: 30-February-2014
Alternate Names:

Gene Info:

Publications:
FoundationOneGenes: MAP2K1
- Version: 03-September-2020
Alternate Names:

Gene Info:

Gene Categories:

CLINICALLY ACTIONABLE

Publications:
CarisMolecularIntelligence: MAP2K1
- Version: 04-September-2020
Alternate Names:

Gene Info:

Gene Categories:

CLINICALLY ACTIONABLE

Publications:
Oncomine: MAP2K1
- Version: v3
Alternate Names:

Gene Info:

Gene Categories:

CLINICALLY ACTIONABLE

Publications:
COSMIC: MAP2K1
- Version: 4-Sep-2020
Alternate Names:

Gene Info:

Gene Categories:

DRUG RESISTANCE

Publications:

Mechanism of Interaction	Dual specificity mitogen-activated protein kinase kinase 1 inhibitor
Direct Interaction	yes

Trial Name	AZD-8330
Novel drug target	Novel Target
Mechanism of Interaction	Dual specificity mitogen-activated protein kinase kinase 1 inhibitor

Specific Action of the Ligand	Negative
Endogenous Drug?	False
Direct Interaction?	True

Indication/Tumor Type	melanoma
Response Type	resistant
Approval Status	Preclinical

Evidence Type	Actionable
Approval Status	Preclinical
Response Type	sensitive

Clinical Status	case report
Pathway	activation
Variant Effect	gain-of-function

combination therapy	Dabrafenib + SCH772984
Indication/Tumor Type	colorectal cancer
Response Type	sensitive

Notes
Mechanism of Interaction	Dual specificity mitogen-activated protein kinase kinase 1 inhibitor
Direct Interaction	yes

Trial Name	WX-554
Novel drug target	Novel Target
Mechanism of Interaction	Dual specificity mitogen-activated protein kinase kinase 1 inhibitor

combination therapy	Panitumumab + Trametinib
Indication/Tumor Type	colorectal cancer
Response Type	sensitive

combination therapy	Ceritinib + Selumetinib
Indication/Tumor Type	non-small cell lung carcinoma
Response Type	sensitive

combination therapy	Vemurafenib + Cetuximab
Indication/Tumor Type	colorectal cancer
Response Type	sensitive

Response Type	conflicting
Response Type	no benefit
combination therapy	GSK2126458 + Trametinib

Q02750	Uniprot Accession
MP2K1_HUMAN	Uniprot Id
5604	Entrez Gene Id

DUAL SPECIFICITY MITOGEN-ACTIVATED PROTEIN KINASE KINASE 1 (EC 2.7.1.-) (MAP KINASE KINASE 1) (MAPKK 1) (ERK ACTIVATOR KINASE 1) (MAPK/ERK KINASE 1) (MEK1). [SOURCE:UNIPROT/SWISSPROT;ACC:Q02750]	Description
ENSG00000169032	Ensembl Gene Id
MAP2K1	Display Id

6840	HUGO Gene ID
6840	HUGO Gene Symbol
mitogen-activated protein kinase kinase 1	HUGO Gene Name

5604	OncoKB Entrez Id
MKK1	OncoKB Gene Synonym
PRKMK1	OncoKB Gene Synonym

Dual specificity mitogen-activated protein kinase kinase 1	Gene Name
Q02750	UniProt ID

MAP2K1 Gene Record

MAP2K1 5604 Druggable GenomeClinically ActionableDrug Resistance

Alternate Names:

Gene Info:

Gene Categories: Category Details

Publications:

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Mechanism of Interaction Dual specificity mitogen-activated protein kinase kinase 1 inhibitor Direct Interaction yes

PMIDs: 25766633

Sources: DTC ChemblInteractions

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Trial Name AZD-8330 Novel drug target Novel Target Mechanism of Interaction Dual specificity mitogen-activated protein kinase kinase 1 inhibitor

PMIDs: None found

Sources: TdgClinicalTrial ChemblInteractions

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Reported Cancer Type Melanoma

PMIDs: None found

Sources: CancerCommons

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 20053779

Sources: DTC

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Reported Cancer Type Melanoma

PMIDs: None found

Sources: CancerCommons

Interaction Types & Directionality: allosteric modulator inhibitor (inhibitory)

Interaction Info: Specific Action of the Ligand Negative Endogenous Drug? False Direct Interaction? True

PMIDs: 26582713

Sources: MyCancerGenome JAX-CKB ChemblInteractions GuideToPharmacology CancerCommons

Interaction Types & Directionality: allosteric modulator inhibitor (inhibitory)

Interaction Info: Direct Interaction yes Mechanism of Interaction Dual specificity mitogen-activated protein kinase kinase 1 inhibitor Novel drug target Novel Target

PMIDs: 26566875 26384788

Sources: TALC MyCancerGenome TdgClinicalTrial ClearityFoundationClinicalTrial JAX-CKB ChemblInteractions GuideToPharmacology CancerCommons MyCancerGenomeClinicalTrial OncoKB

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Indication/Tumor Type melanoma Response Type resistant Approval Status Preclinical

PMIDs: 26582713 26267534 25766633 23398453 10592235

Sources: DTC MyCancerGenome JAX-CKB ChemblInteractions

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Mechanism of Interaction Dual specificity mitogen-activated protein kinase kinase 1 inhibitor Direct Interaction yes Details of the Assay for Interaction Measured in a fluorescence anisotropy assay using recombinant MEK1. Ki approximated from the graph in supplementary figure 1b.

PMIDs: None found

Sources: MyCancerGenome ChemblInteractions GuideToPharmacology

Interaction Types & Directionality: allosteric modulator inhibitor (inhibitory)

Interaction Info: Specific Action of the Ligand Negative Endogenous Drug? False Direct Interaction? True

PMIDs: 26324360 19915144 18632602 25394791 27312529 22197931 26582713 22327936 24448821 23444215 17332304 28029918 17699718

Sources: TALC MyCancerGenome ClearityFoundationClinicalTrial JAX-CKB ChemblInteractions COSMIC CIViC GuideToPharmacology CancerCommons MyCancerGenomeClinicalTrial TTD

Interaction Types & Directionality: allosteric modulator inhibitor (inhibitory)

Interaction Info: Direct Interaction yes Mechanism of Interaction Dual specificity mitogen-activated protein kinase kinase 1 inhibitor Reported Cancer Type Melanoma

PMIDs: None found

Sources: MyCancerGenome ClearityFoundationClinicalTrial ChemblInteractions GuideToPharmacology CancerCommons

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Evidence Type Actionable Approval Status Preclinical Response Type sensitive

PMIDs: 24448821

Sources: JAX-CKB ChemblInteractions GuideToPharmacology

Interaction Types & Directionality: antagonist (inhibitory) inhibitor (inhibitory)

Interaction Info: Trial Name GSK1120212 Novel drug target Novel Target Notes

PMIDs: 23432625 26566875 26644315 25370473 22389471 26582713 24265154 28179366 24265153 27312529 25673644 25899310 24982505

Sources: TALC MyCancerGenome TdgClinicalTrial ClearityFoundationClinicalTrial JAX-CKB CGI CIViC GuideToPharmacology MyCancerGenomeClinicalTrial OncoKB

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Mechanism of Interaction Dual specificity mitogen-activated protein kinase kinase 1 inhibitor Direct Interaction yes

PMIDs: None found

Sources: ChemblInteractions

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Mechanism of Interaction Dual specificity mitogen-activated protein kinase kinase 1 inhibitor Direct Interaction yes

PMIDs: None found

Sources: ChemblInteractions

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Mechanism of Interaction Dual specificity mitogen-activated protein kinase kinase; MEK1/2 inhibitor Direct Interaction yes

PMIDs: None found

Sources: ChemblInteractions

Interaction Types & Directionality: n/a

Interaction Info: Indication/Tumor Type melanoma Response Type sensitive Approval Status Preclinical - Cell culture

PMIDs: 26267534

Sources: JAX-CKB

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Mechanism of Interaction Dual specificity mitogen-activated protein kinase kinase 1 inhibitor Direct Interaction yes

PMIDs: None found

Sources: ChemblInteractions

Interaction Types & Directionality: n/a

Interaction Info: Clinical Status case report Pathway activation Variant Effect gain-of-function

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Dual specificity mitogen-activated protein kinase kinase 1 inhibitor

Direct Interaction yes

PMIDs:
25766633

Sources:
DTC ChemblInteractions

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Trial Name AZD-8330

Novel drug target Novel Target

Mechanism of Interaction Dual specificity mitogen-activated protein kinase kinase 1 inhibitor

PMIDs:
None found

Sources:
TdgClinicalTrial ChemblInteractions

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Reported Cancer Type Melanoma

PMIDs:
None found

Sources:
CancerCommons

Interaction Types & Directionality:

n/a

PMIDs:
20053779

Sources:
DTC

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Reported Cancer Type Melanoma

PMIDs:
None found

Sources:
CancerCommons

Interaction Types & Directionality:

allosteric modulator

inhibitor (inhibitory)

Interaction Info:

Specific Action of the Ligand Negative

Endogenous Drug? False

Direct Interaction? True

PMIDs:
26582713

Sources:
MyCancerGenome JAX-CKB ChemblInteractions GuideToPharmacology CancerCommons

Interaction Types & Directionality:

allosteric modulator

inhibitor (inhibitory)

Interaction Info:

Direct Interaction yes

Mechanism of Interaction Dual specificity mitogen-activated protein kinase kinase 1 inhibitor

Novel drug target Novel Target

PMIDs:
26566875 26384788

Sources:
TALC MyCancerGenome TdgClinicalTrial ClearityFoundationClinicalTrial JAX-CKB ChemblInteractions GuideToPharmacology CancerCommons MyCancerGenomeClinicalTrial OncoKB

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Indication/Tumor Type melanoma

Response Type resistant

Approval Status Preclinical

PMIDs:
26582713 26267534 25766633 23398453 10592235

Sources:
DTC MyCancerGenome JAX-CKB ChemblInteractions

Interaction Types & Directionality:

inhibitor (inhibitory)

PMIDs:
None found

Sources:
MyCancerGenome ChemblInteractions GuideToPharmacology

Interaction Types & Directionality:

allosteric modulator

inhibitor (inhibitory)

Interaction Info:

Specific Action of the Ligand Negative

Endogenous Drug? False

Direct Interaction? True

PMIDs:
26324360 19915144 18632602 25394791 27312529 22197931 26582713 22327936 24448821 23444215 17332304 28029918 17699718

Sources:
TALC MyCancerGenome ClearityFoundationClinicalTrial JAX-CKB ChemblInteractions COSMIC CIViC GuideToPharmacology CancerCommons MyCancerGenomeClinicalTrial TTD

Interaction Types & Directionality:

allosteric modulator

inhibitor (inhibitory)

Interaction Info:

Direct Interaction yes

Mechanism of Interaction Dual specificity mitogen-activated protein kinase kinase 1 inhibitor

Reported Cancer Type Melanoma

PMIDs:
None found

Sources:
MyCancerGenome ClearityFoundationClinicalTrial ChemblInteractions GuideToPharmacology CancerCommons

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Evidence Type Actionable

Approval Status Preclinical

Response Type sensitive

PMIDs:
24448821

Sources:
JAX-CKB ChemblInteractions GuideToPharmacology

Interaction Types & Directionality:

antagonist (inhibitory)

inhibitor (inhibitory)

Interaction Info:

Trial Name GSK1120212

Novel drug target Novel Target

Notes

PMIDs:
23432625 26566875 26644315 25370473 22389471 26582713 24265154 28179366 24265153 27312529 25673644 25899310 24982505

Sources:
TALC MyCancerGenome TdgClinicalTrial ClearityFoundationClinicalTrial JAX-CKB CGI CIViC GuideToPharmacology MyCancerGenomeClinicalTrial OncoKB

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Dual specificity mitogen-activated protein kinase kinase 1 inhibitor

Direct Interaction yes

PMIDs:
None found

Sources:
ChemblInteractions

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Dual specificity mitogen-activated protein kinase kinase 1 inhibitor

Direct Interaction yes

PMIDs:
None found

Sources:
ChemblInteractions

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Dual specificity mitogen-activated protein kinase kinase; MEK1/2 inhibitor

Direct Interaction yes

PMIDs:
None found

Sources:
ChemblInteractions

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type melanoma

Response Type sensitive

Approval Status Preclinical - Cell culture

PMIDs:
26267534

Sources:
JAX-CKB

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Dual specificity mitogen-activated protein kinase kinase 1 inhibitor

Direct Interaction yes

PMIDs:
None found

Sources:
ChemblInteractions

Interaction Types & Directionality:

n/a

Interaction Info:

Clinical Status case report

Pathway activation

Variant Effect gain-of-function

PMIDs:
22197931 19915144 25157968 18632602 7651428 23569304 21383288 22389471 24448821 24265153 27312529

Sources:
JAX-CKB CGI DoCM CIViC

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Dabrafenib + SCH772984

Indication/Tumor Type colorectal cancer

Response Type sensitive

PMIDs:
24463458 25370473 22389471 24265154 24265153 27312529 25673644

Sources:
JAX-CKB CIViC

Interaction Types & Directionality:

allosteric modulator

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Dual specificity mitogen-activated protein kinase kinase 1 inhibitor

Direct Interaction yes

Specific Action of the Ligand Negative