MI-77301 (SAR405838)

Cas No.:	1303607-60-4
Chemical Name:	MI-773 (SAR405838)
Synonyms:	MI-773 (SAR405838);(2'S,3'R,4'S,5'R)-6-chloro-4'-(3-chloro-2-fluoro-phenyl)-2'-(2,2-dimethyl-propyl)-2-oxo-1,2-dihydro-spiro [indole-3,3'-pyrrolidine]-5'-carboxylic acid (trans-4-hydroxy-cyclohexyl)-amide;MI-77301;SAR405838;SAR405838 (MI-773);(2'S,3R,4'S,5'R)-6-Chloro-4'-(3-chloro-2-fluorophenyl)-2'-(2,2-dimethylpropyl)-1,2-dihydro-N-(trans-4-hydroxycyclohexyl)-2-oxo-spiro[3H-indole-3,3'-pyrrolidine]-5'-carboxamide;MI 77301
SMILES:	O=C([C@H](N[C@H]1CC(C)(C)C)[C@H](C2=CC=CC(Cl)=C2F)[C@@]31C(NC4=C3C=CC(Cl)=C4)=O)N[C@@H]5CC[C@@H](O)CC5
Formula:	C29N3O3FCl2H34
M.Wt:	562.503
Purity:	>98%
Sotrage:	2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO

Description:

SAR405838 is a highly potent and selective MDM2 inhibitor, binds to MDM2 with Ki= 0.88 nM and has high specificity over other proteins.IC50 value: 0.88 nM (Ki) [1]Target: MDM2in vitro: SAR405838 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.[1] 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.[2]in vivo: 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,). [1]

References:

[1]. Wang S, et al. SAR405838: an optimized inhibitor of MDM2-p53 interaction that induces complete and durable tumor regression. Cancer Res. 2014 Oct 15;74(20):5855-5865. [2]. Hoffman-Luca CG, et al. Elucidation of Acquired Resistance to Bcl-2 and MDM2 Inhibitors in Acute Leukemia In Vitro and In Vivo. Clin Cancer Res. 2015 Jun 1;21(11):2558-2568.