Monday, August 10, 2015

Drugs in Clinical Pipeline: Savolitinib

Savolitinib [(S)-1-(1-(imidazo[1,2-a]pyridin-6-yl)ethyl)-6-(1-methyl-1H-pyrazol-4-yl)-1H-[1,2,3]triazolo[4,5-b]pyrazine] is an orally available, small-molecule, highly selective c-Met inhibitor (IC50 = 0.005 uM). The structure-activity relationship in a series of novel triazolopyrazine c-Met inhibitors was investigated, leading to the identification of Savolitinib, which demonstrated favorable pharmacokinetic properties in mice and good antitumor activities in the human glioma xenograft model in athymic nude mice. Savolitinib is a potent ATP-competitive c-Met inhibitor with high selectivity over a 274-kinase panel. It is being developed as an oral tablet for the treatment of solid tumors [1].

In December 2011, AstraZeneca and Hutchison Medi Pharma have signed a global licensing, co-development, and commercialization agreement for Savolitinib.

The activity of Savolitinib is as follows:

IC50 (c-Met enzyme assay) = 0.005 uM
IC50 (p-Met Cell Based assay) = 0.003 uM

Common Name: Savolitinib
Synonyms: HMPL-504; HMPL 504; HMPL504; AZD6094; AZD-6094; AZD 6094; Volitinib
IUPAC Name: (S)-1-(1-(imidazo[1,2-a]pyridin-6-yl)ethyl)-6-(1-methyl-1H-pyrazol-4-yl)-1H-[1,2,3]triazolo[4,5-b]pyrazine
CAS Number: 1313725-88-0
Mechanism of Action: Kinase Inhibitor; c-Met Inhibitor
Indication: Various Cancers; Solid Tumors
Development Stage: Phase II
Company: Hutchison Medi Pharma (China)/AstraZeneca

1. Jia, H.; et. al. Discovery of (S)-1-(1-(Imidazo[1,2-a]pyridin-6-yl)ethyl)-6-(1-methyl-1H-pyrazol-4-yl)-1H-[1,2,3]triazolo[4,5-b]pyrazine (volitinib) as a highly potent and selective mesenchymal-epithelial transition factor (c-Met) inhibitor in clinical development for treatment of cancer. J Med Chem 2014, 57(18), 7577-7589.