BMS-754807

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

BMS-754807 (BMS 754807, BMS754807) 是一种有效、可逆、口服活性的 IGF-1R/胰岛素受体抑制剂，IC50 分别为 1.8 和 1.7 nM。

BMS-754807 (BMS 754807, BMS754807)?is a potent, reversible, orally active inhibitor of IGF-1R/Insulin receptor with IC50 of 1.8 and 1.7 nM, respectively; shows additional off-target activities Met, RON, TrkA, TrkB, AurA, and AurB (IC50=5-45 nM) in a panel of 27 kinases; inhibits the growth of a broad range of human tumor types in vitro (IC50=5-365 nM), induces PARP and Caspase 3 cleavage, promotes apoptosis; exhibits tumor growth inhibition in xenograft tumor models.Breast Cancer Phase 2 Discontinued(In Vitro):BMS-754807 effectively inhibits the growth of a broad range of human tumor cell lines with IC50 values of ranging from 5 to 365 nM. BMS-754807 also inhibits the proliferation of human rhabdomyosarcoma tumor cells Rh41 and human colon carcinoma Geo with IC50s of 7 and 5 nM, respectively. BMS-754807 shows inhibitory activity in the proliferation of Rh41 cells with IC50 of 5 nM. BMS-754807 inhibits the phosphorylation of IGF-1R (IC50=13 nM) and the downstream targets Akt (IC50=22 nM) and MAPK (IC50=13 nM) in the IGF-Sal cell line with IC50 consistent with the antiproliferative IC50 (7 nM) in this cell line. BMS-754807 shows a median EC50 value of 0.62 μM against the PPTP cell lines. The median EC50 for the four Ewing sarcoma cell lines is less than that for the remaining PPTP cell lines (0.19 μM vs. 0.78 μM, P=0.0470). BMS-754807 (0.25 and 0.5 μM) reduces the activated IGF-IR/IR (pIGF-IR/IR), causes a concurrent decrease in phosphorylated AKT in both lung cancer cell lines. BMS-754807 (0.5 μM) also reduces wound closure of lung cancer cells and reduces the ERK phosphorylation. BMS-754807 reduces cell viability in both A549 and NCI-H358 cells, with IC50 of 1.08 μM and 76 μM, respectively. (In Vivo):BMS-754807 (3.125 and 12.5 mg/kg, p.o.) inhibits tumor growth in IGF-1R-Sal tumor-bearing nude mice. BMS-754807 inhibits tumor growth in a selected group of epithelial (IGF-1R-Sal, GEO, and Colo205), hematopoietic (JJN3), and mesenchymal (RD1 and Rh41) xenograft tumor models with TGI ranging from 53% to 115%. BMS-754807 is effective at a dose level of 3.125 mg/kg twice daily and as low as 6.25 mg/kg once daily, in the highly sensitive Rh41 rhabdomyosarcoma. BMS-754807 (25 mg/kg) also shows synergy when combined with targeted agents in human tumor cell lines and human xenograft models. Furthmore, BMS-754807 is active at doses from 3 mg/kg upward in the IGF-Sal tumor model. BMS-754807 (25 mg/kg, p.o.) induces significant differences in EFS distribution compared to controls in 18 of 32 evaluable solid tumor xenografts (56%) tested, but in none of the ALL xenografts studied.

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BMS 754807 | BMS754807

Angiogenesis

IGF-1R

IGF-1R|InsulinReceptor|Met|TrkA|TrkB

Cancer

Breast Cancer

1001350-96-4

461.4948

C23H24FN9O

>98% (HPLC)

10 mM in DMSO

C[C@]1(CCCN1C2=NN3C=CC=C3C(=N2)NC4=NNC(=C4)C5CC5)C(=O)NC6=CN=C(C=C6)F

2-Pyrrolidinecarboxamide, 1-[4-[(5-cyclopropyl-1H-pyrazol-3-yl)amino]pyrrolo[2,1-f][1,2,4]triazin-2-yl]-N-(6-fluoro-3-pyridinyl)-2-methyl-, (2S)-

(-20℃)

With Ice Pack

≥ 2 years