GSK1904529A

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

GSK1904529A 是 IGF-1R 和 IR 的选择性抑制剂，IC50 分别为 27 nM 和 25 nM。

GSK1904529A is a selective inhibitor of IGF-1R and IR with IC50 of 27 nM and 25 nM, >100-fold more selective for IGF-1R/InsR than Akt1/2, Aurora A/B,B-Raf, CDK2, EGFR etc.

GSK1904529A displays high affinities for IGF-1R and IR, with Kis of 1.6 and 1.3 nM, respectively.GSK1904529A (72 h) inhibits tumor cells proliferation with IC50s ranges from 35 nM to >30 μM, and Ewing's sarcoma and multiple myeloma cell lines are greatest sensitive.GSK1904529A (0.03-3 μM; 24 and 48 h) arrests cells at the G1 phase of the cell cycle.GSK1904529A (2 h) inhibits phosphorylation of IGF-IR and IR with IC50s of 22 and 19 nM in NIH-3T3/LISN and NIH-3T3-hIR cells, respectively.GSK1904529A (0.01-3 μM; 4 h) blocks the major downstream signal transduction pathways mediated by IGF-IR and IR in NIH-3T3/LISN and NIH-3T3-hIR cells. Cell Cycle Analysis Cell Line:COLO 205, MCF-7, and NCI-H929 cells Concentration:0, 0.03, 0.1, 0.3, 1, 3 μM Incubation Time:24 and 48 hours Result:Increased the accumulation in G1 and decreased accumulation in S and G2-M phases of the cell cycle.Western Blot Analysis Cell Line:NIH-3T3/LISN and NIH-3T3-hIR cells Concentration:0.01, 0.03, 0.1, 0.3, 1, 3 μM Incubation Time:4 hours Result:Inhibited the ligand-induced phosphorylation of IGF-IR and IR at concentrations >0.01 μM.Decreased the phosphorylation of AKT, IRS-1, and ERK.

GSK1904529A (30 mg/kg; p.o. once or twice daily for 21 d) has antitumor activity in mice.GSK1904529A (1-30 mg/kg; a single p.o.) decreases IGF-I-induced IGF-IR phosphorylation in a dose-dependent manner in mice.GSK1904529A (30 mg/kg; p.o. once or twice daily for 21 d) has no significant alterations in the blood glucose levels in mice. Animal Model:Female athymic nu/nu CD-1 mice are bring NIH-3T3/LISN tumor 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.

GSK-4529 | GSK1904529a | GSK 1904529 | GSK-1904529a

Angiogenesis

IGF-1R

IGF-1R| Insulin Receptor| B-Raf (V600E)| Syk| VEGFR2

Cancer

——

1089283-49-7

851.96

C44H47F2N9O5S

>98% (HPLC)

DMSO:124 mg/mL (145.54 mM); Ethanol:<1 mg/mL (<1 mM); Water：<1 mg/mL (<1 mM)

O=C(NC1=C(F)C=CC=C1F)C2=CC(C3=C(C4=NC(NC5=CC(CC)=C(N6CCC(N7CCN(S(=O)(C)=O)CC7)CC6)C=C5OC)=NC=C4)N8C=CC=CC8=N3)=CC=C2OC

N-(2,6-Difluorophenyl)-5-[3-[2-[[5-ethyl-2-(methyloxy)-4-[4-[4-(methylsulfonyl)-1-piperazinyl]-1-piperidinyl]phenyl]amino]-4-pyrimidinyl]imidazo[1,2-a]pyridin-2-yl]-2-(methyloxy)benzamide

(-20℃)

With Ice Pack

≥ 2 years