| Target Validation Information | |||||
|---|---|---|---|---|---|
| TTD ID | T99031 | ||||
| Target Name | ERK activator kinase (MEK) | ||||
| Type of Target |
Successful |
||||
| Drug Potency against Target | PD-0325901 | Drug Info | IC50 = 0.34 nM | [1] | |
| Selumetinib | Drug Info | IC50 = 14 nM | [2] | ||
| Action against Disease Model | Selumetinib | Drug Info | AZD6244 is effective in colorectal cancer cell lines with BRAF or KRAS mutations. Sensitivity to MEK1/2 inhibition correlates with a biochemical signature; those cells with highERK1/2 activity (whether mutant for BRAF or KRAS) evolve a dependency upon that pathway and tend to be sensitive to AZD6244 but this can be offset by high PI3K-dependent signalling. | [3] | |
| References | |||||
| REF 1 | Progress towards therapeutic small molecule MEK inhibitors for use in cancer therapy. Curr Top Med Chem. 2005;5(2):215-29. | ||||
| REF 2 | Therapeutic strategies for inhibiting oncogenic BRAF signaling. Curr Opin Pharmacol. 2008 Aug;8(4):419-26. | ||||
| REF 3 | Intrinsic resistance to the MEK1/2 inhibitor AZD6244 (ARRY-142886) is associated with weak ERK1/2 signalling and/or strong PI3K signalling in colorectal cancer cell lines. Int J Cancer. 2009 Nov 15;125(10):2332-41. | ||||
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