Saturday, April 4, 2015

Drugs in Clinical Pipeline: Selumetinib

Selumetinib [6-(4-bromo-2-chloroanilino)-7-fluoro-N-(2-hydroxyethoxy)-3-methylbenzimidazole-5-carboxamideis a potent and selective inhibitor of MEK1 and 2 that is currently being clinically developed for the treatment of several human malignancies. Selumetinib is a potent, highly selective MEK1 inhibitor with IC50 of 14 nM, also inhibits ERK1/2 phosphorylation with IC50 of 10 nM, no inhibition to p38a, MKK6, EGFR, ErbB2, ERK2, B-Raf, etc.

It is developed by Array Biopharma and licensed to AstraZeneca. AstraZeneca is responsible for further development and commercialization of Selumetinib.

MEK is a key protein kinase in the RAS/RAF/MEK/ERK pathway, which regulates several key cellular activities including proliferation, differentiation, migration, survival and angiogenesis. Inappropriate activation of this pathway has been shown to occur in many cancers, in particular through mutations in BRAF, KRAS and NRAS. Selumetinib could be particularly effective in tumors with a hyperactivated Ras/Raf/MEK/ERK pathway, which might be the case of KRAS-mutant non-small-cell lung cancers (NSCLCs).

Common Name: Selumetinib

Synonyms: ARRY-142886; AZD6244
IUPAC Name: 6-(4-bromo-2-chloroanilino)-7-fluoro-N-(2-hydroxyethoxy)-3-methyl benzimidazole-5-carboxamide
CAS Number: 606143-52-6
Mechanism of Action: Kinase Inhibitior; MEK Inhibitor
Indication: Various Cancers; Non-Small Cell Lung Cancer
Development Stage: Phase III
Company: Array Biopharma/AstraZeneca

1. 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). NCT01933932
2. Selumetinib (AZD6244: ARRY-142886) (Hyd-Sulfate) in Metastatic Uveal Melanoma (SUMIT). NCT01974752