AMG-47a

AMG 47a is an orally bioavailable inhibitor of Lck, VEGF receptor 2 (VEGFR2/KDR), p38α, and JAK3 (IC₅₀s = 0.2, 1, 3, and 72 nM, respectively). It is selective for these kinases over a panel of additional kinases including SYK, JNK1, and PKAβ (IC₅₀s = 292 to >25,000 nM) but does inhibit Src (IC₅₀ = 2 nM). It decreases IL-2, but not TNF-α, production induced by an anti-CD3 antibody in 50% whole blood and inhibits T cell proliferation in vitro in a mixed lymphocyte reaction assay (IC₅₀ = 30 nM). AMG 47a (10, 30, and 100 mg/kg) has anti-inflammatory activity, decreasing production of IL-2 induced by an anti-CD3 antibody in mice. It also decreases levels of mutant oncogene KRAS^G12V in HeLa cells in a reporter assay when used at a concentration of 1 μM.

AMG-47a is a inhibitor of lymphocyte-specific kinase (Lck), which is a cytoplasmic tyrosine kinase of the Src family expressed in T cells and natural killer (NK) cells.

1. carver j, dexheimer ts, hsu d et al. a high-throughput assay for small molecule destabilizers of the krasoncoprotein. plos one. 2014 aug 5;9(8):e103836.