GSK1904529A is a small-molecule inhibitor of the insulin-like growth factor-I receptor (IGF-IR) with IC50 value of 27 nM 1.
GSK1904529A is a reversible and ATP-competitive inhibitor with Ki value of 1.6 nM. In NIH-3T3/LISN cells, GSK1904529A potently inhibited phosphorylation of IGF-IR with IC50 value of 22 nM. It also demonstrated to be a selective inhibitor since it showed poor inhibitory activity against 45 other serine/threonine and tyrosine kinases. When treated with whole-cell extracts, GSK1904529A significantly inhibited the ligand-induced phosphorylation of IGF-IR and decreased phosphorylation of downstream signaling including AKT, IRS-1 and ERK at concentrations > 0.01μM. GSK1904529A suppressed cell proliferation in a variety of tumor cells. The IC50 values for NCI-H929, TC-71, SK-N-MC, COLO 205, MCF7 and PREC are 81, 35, 43, 124, 137 and 68 nM, respectively. In COLO 205, MCF-7, and NCI-H929 cells, GSK1904529A treatment resulted in cell accumulation in G1 and decrease in S and G2-M phases. Moreover, in NIH-3T3/LISN xenograft model, once daily administration of GSK1904529A at 30 mg/kg inhibited 56% of tumor growth 1.
1. Sabbatini P, Rowand J L, Groy A, et al. Antitumor activity of GSK1904529A, a small-molecule inhibitor of the insulin-like growth factor-I receptor tyrosine kinase. Clinical Cancer Research, 2009, 15(9): 3058-3067.