GSK1904529A

The Uses of GSK1904529A

A selective inhibitor of IGF-1R and IR with IC50s of 27 nM and 25 nM, respectively.

The Uses of GSK1904529A

GSK 1904529A is a small-molecule inhibitor of the insulin-like growth factor-I receptor tyrosine kinase.

Definition

ChEBI: N-(2,6-difluorophenyl)-5-[3-[2-[5-ethyl-2-methoxy-4-[4-(4-methylsulfonyl-1-piperazinyl)-1-piperidinyl]anilino]-4-pyrimidinyl]-2-imidazo[1,2-a]pyridinyl]-2-methoxybenzamide is a member of benzamides.

Biological Activity

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.

References

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.