| 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
|
[5], [6], [8] |
| Mutation Prevalence |
16% of the patients |
|
| Mutation Info |
Missense: D67N |
| Drugs |
|
| Mutation Info |
Missense: E120D |
| Drugs |
|
| Mutation Info |
Missense: E203K |
| Drugs |
|
| Mutation Info |
Missense: F129L |
| Drugs |
| Drug Name |
PD0325901 |
Drug Info
|
[1] |
| Targeted Disease |
Cancer; Non-small Cell Lung Cancer |
|
|
|
| Mutation Info |
Missense: F133L |
| Drugs |
|
| Mutation Info |
Missense: G128D |
| Drugs |
| Drug Name |
Dabrafenib |
Drug Info
|
[3] |
| Targeted Disease |
Melanoma |
| Mutation Prevalence |
1 out of 10 patients |
|
|
|
| Mutation Info |
Missense: G128V |
| Drugs |
| Drug Name |
Vemurafenib |
Drug Info
|
[2] |
| Mutation Prevalence |
1 out of 76 patients |
|
| Mutation Info |
Missense: H119P |
| Drugs |
|
| Mutation Info |
Missense: I103N |
| Drugs |
|
| Mutation Info |
Missense: I111N |
| Drugs |
|
| Mutation Info |
Missense: I99T |
| Drugs |
|
| Mutation Info |
Missense: K104N |
| Drugs |
|
| Mutation Info |
Missense: K57E |
| Drugs |
| Drug Name |
Dabrafenib |
Drug Info
|
[4] |
| Targeted Disease |
Melanoma |
| Mutation Prevalence |
1 out of 30 patients |
|
|
|
| Mutation Info |
Missense: K57N |
| Drugs |
|
| Mutation Info |
Missense: L115P |
| Drugs |
| Drug Name |
PD0325901 |
Drug Info
|
[1] |
| Targeted Disease |
Cancer; Non-small Cell Lung Cancer |
|
| Mutation Info |
Missense: L215P |
| Drugs |
|
| Mutation Info |
Missense: P124L |
| Drugs |
|
| Drug Name |
Vemurafenib |
Drug Info
|
[2] |
| Mutation Prevalence |
1 out of 76 patients |
|
|
|
| Mutation Info |
Missense: P124S |
| Drugs |
| Drug Name |
Dabrafenib |
Drug Info
|
[2] |
| Targeted Disease |
Melanoma |
| Mutation Prevalence |
1 out of 76 patients |
|
| Drug Name |
PLX4720 |
Drug Info
|
[5], [6] |
| Targeted Disease |
Cutaneous Melanoma |
|
|
|
| Mutation Info |
Missense: Q56P |
| Drugs |
| Drug Name |
PLX4720 |
Drug Info
|
[5], [6] |
| Targeted Disease |
Cutaneous Melanoma |
|
|
|
| Mutation Info |
Missense: V211D |
| Drugs |
|
| Mutation Info |
Missense: V60E |
| Drugs |
| Drug Name |
Vemurafenib |
Drug Info
|
[2] |
| Mutation Prevalence |
1 out of 76 patients |
|
| References |
| REF 1 |
ERK inhibition overcomes acquired resistance to MEK inhibitors. Mol Cancer Ther. 2012 May;11(5):1143-54.
|
| REF 2 |
The genetic landscape of clinical resistance to RAF inhibition in metastatic melanoma. Cancer Discov. 2014 Jan;4(1):94-109.
|
| REF 3 |
Increased MAPK reactivation in early resistance to dabrafenib/trametinib combination therapy of BRAF-mutant metastatic melanoma. Nat Commun. 2014 Dec 2;5:5694.
|
| REF 4 |
BRAF inhibitor resistance mechanisms in metastatic melanoma: spectrum and clinical impact. Clin Cancer Res. 2014 Apr 1;20(7):1965-77.
|
| REF 5 |
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 6 |
Dissecting therapeutic resistance to RAF inhibition in melanoma by tumor genomic profiling. J Clin Oncol. 2011 Aug 1;29(22):3085-96.
|
| REF 7 |
Pharmacodynamic effects and mechanisms of resistance to vemurafenib in patients with metastatic melanoma. J Clin Oncol. 2013 May 10;31(14):1767-74.
|
| REF 8 |
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.
|
