Resistance mutation info of target

Target General Information
Target ID T35940
Target Name Dual specificity mitogen-activated protein kinase kinase 1 (MAP2K1) Target Info
Gene Name MAP2K1
Species Homo sapiens
Uniprot ID MP2K1_HUMAN
Sequence MPKKKPTPIQLNPAPDGSAVNGTSSAETNLEALQKKLEELELDEQQRKRLEAFLTQKQKV
GELKDDDFEKISELGAGNGGVVFKVSHKPSGLVMARKLIHLEIKPAIRNQIIRELQVLHE
CNSPYIVGFYGAFYSDGEISICMEHMDGGSLDQVLKKAGRIPEQILGKVSIAVIKGLTYL
REKHKIMHRDVKPSNILVNSRGEIKLCDFGVSGQLIDSMANSFVGTRSYMSPERLQGTHY
SVQSDIWSMGLSLVEMAVGRYPIPPPDAKELELMFGCQVEGDAAETPPRPRTPGRPLSSY
GMDSRPPMAIFELLDYIVNEPPPKLPSGVFSLEFQDFVNKCLIKNPAERADLKQLMVHAF
IKRSDAEEVDFAGWLCSTIGLNQPSTPTHAAGV [Homo sapiens]
Drug Resistance Mutation and Corresponding Drugs
Ref 1572597Targeting BRAFV600E with PLX4720 displays potent antimigratory and anti-invasive activity in preclinical models of human thyroid cancer.
Ref 524363ClinicalTrials.gov (NCT01898585) An Open-Label Study of Zelboraf (Vemurafenib) in Patients With Braf V600 Mutation Positive Metastatic Melanoma. U.S. National Institutes of Health.
Ref 541191(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 5893).
Ref 551871Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
Ref 542850(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7935).
Ref 547954Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800020671)
Ref 537114Emerging therapies for multiple myeloma. Expert Opin Emerg Drugs. 2009 Mar;14(1):99-127.
Ref 541008(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 5665).
Ref 1572593ClinicalTrials.gov (NCT01933932) Assess Efficacy & Safety of Selumetinib in Combination With Docetaxel in Patients Receiving 2nd Line Treatment for v-Ki-ras2 Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) Positive NSCLC (SELECT-1)
Ref 556264Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
Mutation Info Missense: C121S
Drugs
Drug Name AZD6244 Drug Info [555733], [555798], [555926]
Targeted Disease Cutaneous Melanoma
Mutation Prevalence 16% of the patients
Mutation Info Missense: D67N
Drugs
Drug Name AZD6244 Drug Info [555733]
Targeted Disease Cutaneous Melanoma
Mutation Info Missense: E120D
Drugs
Drug Name AZD6244 Drug Info [555733]
Targeted Disease Cutaneous Melanoma
Mutation Info Missense: E203K
Drugs
Drug Name Vemurafenib Drug Info [555935]
Targeted Disease Melanoma
Mutation Info Missense: F129L
Drugs
Drug Name AZD6244 Drug Info [555733]
Targeted Disease Cutaneous Melanoma
Drug Name PD0325901 Drug Info [555849]
Targeted Disease Cancer
Mutation Info Missense: F133L
Drugs
Drug Name AZD6244 Drug Info [555733]
Targeted Disease Cutaneous Melanoma
Mutation Info Missense: G128D
Drugs
Drug Name Dabrafenib Drug Info [556039]
Targeted Disease Melanoma
Mutation Prevalence 1 out of 10 patients
Drug Name AZD6244 Drug Info [555733]
Targeted Disease Cutaneous Melanoma
Mutation Info Missense: G128V
Drugs
Drug Name Vemurafenib Drug Info [555981]
Targeted Disease Melanoma
Mutation Prevalence 1 out of 76 patients
Mutation Info Missense: H119P
Drugs
Drug Name AZD6244 Drug Info [555733]
Targeted Disease Cutaneous Melanoma
Mutation Info Missense: I103N
Drugs
Drug Name AZD6244 Drug Info [555733]
Targeted Disease Cutaneous Melanoma
Mutation Info Missense: I111N
Drugs
Drug Name AZD6244 Drug Info [555733]
Targeted Disease Cutaneous Melanoma
Mutation Info Missense: I99T
Drugs
Drug Name AZD6244 Drug Info [555733]
Targeted Disease Cutaneous Melanoma
Mutation Info Missense: K104N
Drugs
Drug Name AZD6244 Drug Info [555733]
Targeted Disease Cutaneous Melanoma
Mutation Info Missense: K57E
Drugs
Drug Name Dabrafenib Drug Info [555991]
Targeted Disease Melanoma
Mutation Prevalence 1 out of 30 patients
Drug Name Vemurafenib Drug Info [555935]
Targeted Disease Melanoma
Mutation Info Missense: K57N
Drugs
Drug Name AZD6244 Drug Info [555733], [555798], [555926]
Targeted Disease Cutaneous Melanoma
Mutation Info Missense: L115P
Drugs
Drug Name PD0325901 Drug Info [555849]
Targeted Disease Cancer
Mutation Info Missense: L215P
Drugs
Drug Name AZD6244 Drug Info [555733]
Targeted Disease Cutaneous Melanoma
Mutation Info Missense: P124L
Drugs
Drug Name Vemurafenib Drug Info [555981]
Targeted Disease Melanoma
Mutation Prevalence 1 out of 76 patients
Drug Name AZD6244 Drug Info [555733], [555798], [555926]
Targeted Disease Cutaneous Melanoma
Drug Name Selumetinib Drug Info [555733]
Targeted Disease Melanoma
Mutation Info Missense: P124S
Drugs
Drug Name Dabrafenib Drug Info [555981]
Targeted Disease Melanoma
Mutation Prevalence 1 out of 76 patients
Drug Name AZD6244 Drug Info [555733]
Targeted Disease Cutaneous Melanoma
Drug Name PLX4720 Drug Info [555733], [555798]
Targeted Disease Cutaneous Melanoma
Mutation Info Missense: Q56P
Drugs
Drug Name AZD6244 Drug Info [555733]
Targeted Disease Cutaneous Melanoma
Drug Name PLX4720 Drug Info [555733], [555798]
Targeted Disease Cutaneous Melanoma
Mutation Info Missense: V211D
Drugs
Drug Name AZD6244 Drug Info [555733]
Targeted Disease Cutaneous Melanoma
Mutation Info Missense: V60E
Drugs
Drug Name Vemurafenib Drug Info [555981]
Targeted Disease Melanoma
Mutation Prevalence 1 out of 76 patients
Reference
Ref 555733MEK1 mutations confer resistance to MEK and B-RAF inhibition. Proc Natl Acad Sci U S A. 2009 Dec 1;106(48):20411-6. doi: 10.1073/pnas.0905833106. Epub 2009 Nov 13.
Ref 555798Dissecting therapeutic resistance to RAF inhibition in melanoma by tumor genomic profiling. J Clin Oncol. 2011 Aug 1;29(22):3085-96. doi: 10.1200/JCO.2010.33.2312. Epub 2011 Mar 7.
Ref 555849ERK inhibition overcomes acquired resistance to MEK inhibitors. Mol Cancer Ther. 2012 May;11(5):1143-54. doi: 10.1158/1535-7163.MCT-11-1010. Epub 2012 Mar 8.
Ref 555926Phase II trial of MEK inhibitor selumetinib (AZD6244, ARRY-142886) in patients with BRAFV600E/K-mutated melanoma. Clin Cancer Res. 2013 Apr 15;19(8):2257-64. doi: 10.1158/1078-0432.CCR-12-3476. Epub 2013 Feb 26.
Ref 555935Pharmacodynamic effects and mechanisms of resistance to vemurafenib in patients with metastatic melanoma. J Clin Oncol. 2013 May 10;31(14):1767-74. doi: 10.1200/JCO.2012.44.7888. Epub 2013 Apr 8.
Ref 555981The genetic landscape of clinical resistance to RAF inhibition in metastatic melanoma. Cancer Discov. 2014 Jan;4(1):94-109. doi: 10.1158/2159-8290.CD-13-0617. Epub 2013 Nov 21.
Ref 555991BRAF inhibitor resistance mechanisms in metastatic melanoma: spectrum and clinical impact. Clin Cancer Res. 2014 Apr 1;20(7):1965-77. doi: 10.1158/1078-0432.CCR-13-3122. Epub 2014 Jan 24.
Ref 556039Increased MAPK reactivation in early resistance to dabrafenib/trametinib combination therapy of BRAF-mutant metastatic melanoma. Nat Commun. 2014 Dec 2;5:5694. doi: 10.1038/ncomms6694.

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