Target General Information
Target ID	T35940
Target Name	Dual specificity mitogen-activated protein kinase kinase 1 (MAP2K1)
Gene Name	MAP2K1
Species	Homo sapiens
UniProt ID	MP2K1_HUMAN
Sequence	MPKKKPTPIQLNPAPDGSAVNGTSSAETNLEALQKKLEELELDEQQRKRLEAFLTQKQKV GELKDDDFEKISELGAGNGGVVFKVSHKPSGLVMARKLIHLEIKPAIRNQIIRELQVLHE CNSPYIVGFYGAFYSDGEISICMEHMDGGSLDQVLKKAGRIPEQILGKVSIAVIKGLTYL REKHKIMHRDVKPSNILVNSRGEIKLCDFGVSGQLIDSMANSFVGTRSYMSPERLQGTHY SVQSDIWSMGLSLVEMAVGRYPIPPPDAKELELMFGCQVEGDAAETPPRPRTPGRPLSSY GMDSRPPMAIFELLDYIVNEPPPKLPSGVFSLEFQDFVNKCLIKNPAERADLKQLMVHAF IKRSDAEEVDFAGWLCSTIGLNQPSTPTHAAGV [Homo sapiens]
Drug and Corresponding Resistance Mutations
Mutation Info	Missense: C121S
Drugs	Drug Name AZD6244 Drug Info [1], [2], [3] Targeted Disease Melanoma Mutation Prevalence 16% of the patients
	Drug Name AZD6244 Drug Info [1], [2], [3] Targeted Disease Cutaneous Melanoma Mutation Prevalence 16% of the patients
Mutation Info	Missense: D67N
Drugs	Drug Name AZD6244 Drug Info [1] Targeted Disease Melanoma
	Drug Name AZD6244 Drug Info [1] Targeted Disease Cutaneous Melanoma
Mutation Info	Missense: E120D
Drugs	Drug Name AZD6244 Drug Info [1] Targeted Disease Melanoma
	Drug Name AZD6244 Drug Info [1] Targeted Disease Cutaneous Melanoma
Mutation Info	Missense: E203K
Drugs	Drug Name Vemurafenib Drug Info [5] Targeted Disease Melanoma
Mutation Info	Missense: F129L
Drugs	Drug Name AZD6244 Drug Info [1] Targeted Disease Melanoma
	Drug Name PD0325901 Drug Info [6] Targeted Disease Cancer; Non-small Cell Lung Cancer
	Drug Name AZD6244 Drug Info [1] Targeted Disease Cutaneous Melanoma
Mutation Info	Missense: F133L
Drugs	Drug Name AZD6244 Drug Info [1] Targeted Disease Melanoma
	Drug Name AZD6244 Drug Info [1] Targeted Disease Cutaneous Melanoma
Mutation Info	Missense: G128D
Drugs	Drug Name AZD6244 Drug Info [1] Targeted Disease Melanoma
	Drug Name Dabrafenib Drug Info [7] Targeted Disease Melanoma Mutation Prevalence 1 out of 10 patients
	Drug Name AZD6244 Drug Info [1] Targeted Disease Cutaneous Melanoma
Mutation Info	Missense: G128V
Drugs	Drug Name Vemurafenib Drug Info [4] Targeted Disease Melanoma Mutation Prevalence 1 out of 76 patients
Mutation Info	Missense: H119P
Drugs	Drug Name AZD6244 Drug Info [1] Targeted Disease Melanoma
	Drug Name AZD6244 Drug Info [1] Targeted Disease Cutaneous Melanoma
Mutation Info	Missense: I103N
Drugs	Drug Name AZD6244 Drug Info [1] Targeted Disease Melanoma
	Drug Name AZD6244 Drug Info [1] Targeted Disease Cutaneous Melanoma
Mutation Info	Missense: I111N
Drugs	Drug Name AZD6244 Drug Info [1] Targeted Disease Melanoma
	Drug Name AZD6244 Drug Info [1] Targeted Disease Cutaneous Melanoma
Mutation Info	Missense: I99T
Drugs	Drug Name AZD6244 Drug Info [1] Targeted Disease Melanoma
	Drug Name AZD6244 Drug Info [1] Targeted Disease Cutaneous Melanoma
Mutation Info	Missense: K104N
Drugs	Drug Name AZD6244 Drug Info [1] Targeted Disease Melanoma
	Drug Name AZD6244 Drug Info [1] Targeted Disease Cutaneous Melanoma
Mutation Info	Missense: K57E
Drugs	Drug Name Vemurafenib Drug Info [5] Targeted Disease Melanoma
	Drug Name Dabrafenib Drug Info [8] Targeted Disease Melanoma Mutation Prevalence 1 out of 30 patients
Mutation Info	Missense: K57N
Drugs	Drug Name AZD6244 Drug Info [1], [2], [3] Targeted Disease Melanoma
	Drug Name AZD6244 Drug Info [1], [2], [3] Targeted Disease Cutaneous Melanoma
Mutation Info	Missense: L115P
Drugs	Drug Name PD0325901 Drug Info [6] Targeted Disease Cancer; Non-small Cell Lung Cancer
Mutation Info	Missense: L215P
Drugs	Drug Name AZD6244 Drug Info [1] Targeted Disease Melanoma
	Drug Name AZD6244 Drug Info [1] Targeted Disease Cutaneous Melanoma
Mutation Info	Missense: P124L
Drugs	Drug Name Selumetinib Drug Info [1] Targeted Disease Melanoma
	Drug Name AZD6244 Drug Info [1], [2], [3] Targeted Disease Melanoma
	Drug Name Vemurafenib Drug Info [4] Targeted Disease Melanoma Mutation Prevalence 1 out of 76 patients
	Drug Name Selumetinib Drug Info [1] Targeted Disease Cutaneous Melanoma
	Drug Name AZD6244 Drug Info [1], [2], [3] Targeted Disease Cutaneous Melanoma
Mutation Info	Missense: P124S
Drugs	Drug Name AZD6244 Drug Info [1] Targeted Disease Melanoma
	Drug Name Dabrafenib Drug Info [4] Targeted Disease Melanoma Mutation Prevalence 1 out of 76 patients
	Drug Name AZD6244 Drug Info [1] Targeted Disease Cutaneous Melanoma
	Drug Name PLX4720 Drug Info [1], [2] Targeted Disease Cutaneous Melanoma
Mutation Info	Missense: Q56P
Drugs	Drug Name AZD6244 Drug Info [1] Targeted Disease Melanoma
	Drug Name AZD6244 Drug Info [1] Targeted Disease Cutaneous Melanoma
	Drug Name PLX4720 Drug Info [1], [2] Targeted Disease Cutaneous Melanoma
Mutation Info	Missense: V211D
Drugs	Drug Name AZD6244 Drug Info [1] Targeted Disease Melanoma
	Drug Name AZD6244 Drug Info [1] Targeted Disease Cutaneous Melanoma
Mutation Info	Missense: V60E
Drugs	Drug Name Vemurafenib Drug Info [4] Targeted Disease Melanoma Mutation Prevalence 1 out of 76 patients
References
REF 1	MEK1 mutations confer resistance to MEK and B-RAF inhibition. Proc Natl Acad Sci U S A. 2009 Dec 1;106(48):20411-6.
REF 2	Dissecting therapeutic resistance to RAF inhibition in melanoma by tumor genomic profiling. J Clin Oncol. 2011 Aug 1;29(22):3085-96.
REF 3	Phase 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.
REF 4	The genetic landscape of clinical resistance to RAF inhibition in metastatic melanoma. Cancer Discov. 2014 Jan;4(1):94-109.
REF 5	Pharmacodynamic effects and mechanisms of resistance to vemurafenib in patients with metastatic melanoma. J Clin Oncol. 2013 May 10;31(14):1767-74.
REF 6	ERK inhibition overcomes acquired resistance to MEK inhibitors. Mol Cancer Ther. 2012 May;11(5):1143-54.
REF 7	Increased MAPK reactivation in early resistance to dabrafenib/trametinib combination therapy of BRAF-mutant metastatic melanoma. Nat Commun. 2014 Dec 2;5:5694.
REF 8	BRAF inhibitor resistance mechanisms in metastatic melanoma: spectrum and clinical impact. Clin Cancer Res. 2014 Apr 1;20(7):1965-77.

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