SAR-405838

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

SAR-405838(MI-77301, MI-773) 是一种有效的、高选择性的 MDM2-p53 相互作用小分子抑制剂，Ki 为 0.88 nM。

SAR-405838(MI-77301, MI-773) is a potent and highly selective small-molecule inhibitor of MDM2-p53 interaction with Ki of 0.88 nM; activates wild-type p53 in vitro and causes p53-dependent cell-cycle arrest and/or apoptosis; shows durable tumor regression or complete tumor growth inhibition in mouse xenograft models of SJSA-1 osteosarcoma, RS4;11 acute leukemia, LNCaP prostate cancer, and HCT-116 colon cancer; orally bioactive.Blood Cancer Phase 1 Clinical.

SAR405838 (MI-77301) potently inhibits cell growth in cancer cell lines, including SJSA-1 (IC50, 0.092 μM), RS4;11 (IC50, 0.089 μM), LNCaP (IC50, 0.27 μM), and HCT-116 (IC50, 0.20 μM) cells, and displays high selectivity over cancer cell lines with mutated or deleted p53, including SAOS-2 (IC50, >10 μM), PC-3 (IC50, >10 μM), SW620 (IC50, >10 μM), and HCT-116 (p53-/-) (IC50, >20 μM) cells. SAR405838 effectively induces apoptosis in the RS4;11 cell line. SAR405838 potently inhibits cell growth and induces dose-dependent apoptosis in the ABTR1 and ABTR2 sublines, albeit with modestly reduced potency compared with that in the control RS4;11 cell line.

At well-tolerated dose schedules, SAR405838 achieves either durable tumor regression or complete tumor growth inhibition in mouse xenograft models of SJSA-1 osteosarcoma, RS4;11 acute leukemia, LNCaP prostate cancer and HCT-116 colon cancer. Remarkably, a single oral dose of SAR405838 is sufficient to achieve complete tumor regression in the SJSA-1 model. In the SJSA-1 osteosarcoma, acute lymphoblastic leukemia RS4;11, LNCaP prostate cancer, and HCT-116 colon cancer xenograft model, MI-773 (p.o.) effectively inhibits tumor growth in a dose-dependent manner (10 mg/kg, 30 mg/kg, 50 mg/kg, 100 mg/kg, and 200 mg/kg,).

MI-77301 | MI-773

Apoptosis

MDM2-p53

Mdm2

Cancer

Blood cancer

1303607-60-4

562.503

C29H34Cl2FN3O3

>98% (HPLC)

10 mM in DMSO

ClC1=CC=C2C(NC(C23[C@@H](C4=C(F)C(Cl)=CC=C4)[C@H](C(NC5CC[C@@H](O)CC5)=O)N[C@H]3CC(C)(C)C)=O)=C1

Spiro[3H-indole-3,3'-pyrrolidine]-5'-carboxamide, 6-chloro-4'-(3-chloro-2-fluorophenyl)-2'-(2,2-dimethylpropyl)-1,2-dihydro-N-(trans-4-hydroxycyclohexyl)-2-oxo-, (2'S,3R,4'S,5'R)-

(-20℃)

With Ice Pack

≥ 2 years