Uses
GSK 1904529A is a small-molecule inhibitor of the insulin-like growth factor-I receptor tyrosine kinase.
Uses
A selective inhibitor of IGF-1R and IR with IC50s of 27 nM and 25 nM, respectively.
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.
in vivo
GSK1904529A (30 mg/kg; p.o. once or twice daily for 21 d) has antitumor activity in mice[1].
GSK1904529A (1-30 mg/kg; a single p.o.) decreases IGF-I-induced IGF-IR phosphorylation in a dose-dependent manner in mice[1].
GSK1904529A (30 mg/kg; p.o. once or twice daily for 21 d) has no significant alterations in the blood glucose levels in mice[1].
| Animal Model: | Female athymic nu/nu CD-1 mice are bring NIH-3T3/LISN tumor[1] |
| Dosage: | 30 mg/kg |
| Administration: | P.o. once or twice daily for 21 d |
| Result: | Resulted in 56% (once daily) and 98% (twice daily) inhibition of tumor growth.
No significant decrease in body weight on the once-daily schedule.
Observed 11-13% of body weight loss, and recovered to near baseline 6 days after the cessation of treatment in twice-daily group.
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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.
