| 货号 (SKU) | 包装规格 | 是否现货 | 价格 | 数量 |
|---|---|---|---|---|
| B407969-1ml |
1ml |
现货  |
|
| 英文别名 | (S)-1-(4-(5-cyclopropyl-1H-pyrazol-3-ylamino)pyrrolo[1,2-f][1,2,4]triazin-2-yl)-N-(6-fluoropyridin-3-yl)-2-methylpyrrolidine-2-carboxamide |
|---|---|
| 规格或纯度 | Moligand™, 10mM in DMSO |
| 英文名称 | BMS-754807 |
| 生化机理 | BMS-754807 是一种强效、可逆的 IGF-1R/InsR 抑制剂，在无细胞实验中的 IC50 为 1.8 nM/1.7 nM，对 Met (c-Met)、Aurora A/B、TrkA/B 和 Ron 的作用较弱，对 Flt3、Lck、MK2、PKA、PKC 等的活性较低。第 2 阶段 |
| 储存温度 | -80℃储存 |
| 运输条件 | 超低温冰袋运输 |
| 作用类型 | 抑制剂 |
| 作用机制 | 胰岛素受体抑制剂 |
| 产品介绍 |
Information BMS-754807 is a potent and reversible inhibitor ofIGF-1R/InsRwithIC50of 1.8 nM/1.7 nM in cell-free assays, less potent to Met (c-Met), Aurora A/B, TrkA/B and Ron, and shows little activity to Flt3, Lck, MK2, PKA, PKC etc. Phase 2. BMS-754807 effectively inhibits the growth of a broad range of human tumor cell lines of different histologic origins including mesenchymal (Ewing\'s, rhabdomyosarcoma, neuroblastoma, and liposarcoma), epithelial (breast, lung, pancreatic, colon, and gastric), and hematopoietic (multiple myeloma and leukemia), the IC50 values range from 5 nM to 365 nM for the most sensitive cell lines. BMS-754807 inhibits proliferation of IGF-1R-Sal cells and RH41 cells with IC50 of 7 nM and 5 nM. BMS-754807 inhibits phosphorylation of IGF-1R in IGF-1R-Sal cells, Rh41 and Geo with IC50 of 13 nM, 6 nM and 21 nM. BMS-754807 inhibits phosphorylation of Akt in IGF-1R-Sal cells, Rh41 and Geo with IC50 of 22 nM, 13 nM and 16 nM. BMS-754807 induces greater apoptosis in Rh41 cells by 24 hours as indicated by an increased sub-G1 peak (23.1%), compared with control (2.4%). BMS-754807 inhibits the phosphorylation of IGF-1R (IC50 = 13nM) and the downstream targets Akt (IC50 = 22nM) and MAPK (IC50 = 13nM) in the IGF-Sal cell line with IC50 consistent with the antiproliferative IC50 (7 nM) in this cell line. The crystal structure of BMS-754807 cocrystallized with the kinase domain of IGF-1R shows that the donor/acceptor/donor hydrogen bond triad with Met1052 and Glu1050 within the hinge region of the kinase. BMS-754807 shows a median EC50 value of 0.62 μM against 23 cell lines in the pediatric preclinical testing program (PPTP). In vivo BMS-754807 (12.5mg/kg, orally) inhibits IGF-1R phosphorylation in tumor and serum 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 (6.25 mg/kg) achieves complete tumor growth inhibition in the transgenic-derived IGF-Sal tumor mouse model with correlated inhibition of pIGF-1R and pAKT. The protein binding for BMS-754807 ranges from of 98.5% in mouse plasma to 95.9% in human plasma. BMS-754807 results in clearance of 113 (mL/min)/kg, 20 (mL/min)/kg, 3.5 (mL/min)/kg and 41 (mL/min)/kg. BMS-754807 (25\u2009mg/kg) significantly inhibits tumor in KT-5 (Wilms), KT-14 (rhabdoid), Rh28 (rhabdomyosarcoma), and OS-1 xenografts mice model. cell lines： Concentrations：365 nM Incubation Time：72 hours Powder Purity:≥99% |
| 分子类型 | 小分子 |
|---|---|
| Isomeric SMILES | C[C@]1(CCCN1C2=NN3C=CC=C3C(=N2)NC4=NNC(=C4)C5CC5)C(=O)NC6=CN=C(C=C6)F |
| 分子量 | 461.49 |
| Reaxy-Rn | 23979441 |
| Reaxys-RN link address | https://www.reaxys.com/reaxys/secured/hopinto.do?context=S&query=IDE.XRN=23979441&ln= |
| 溶解性 | Solubility (25°C) In vitro DMSO: 34.9 mg/mL (100.51 mM); |
|---|
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