SAR405838

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: MDM2 in 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, ).

Product information

CAS Number: 1303607-60-4

Molecular Weight: 562.50

Formula: C29H34Cl2FN3O3

Chemical Name: SAR405838

Smiles: CC(C)(C)C[C@@H]1N[C@H]([C@H](C2=CC=CC(Cl)=C2F)[C@]21C1=CC=C(Cl)C=C1NC2=O)C(=O)N[C@@H]1CC[C@@H](O)CC1

InChiKey: IDKAKZRYYDCJDU-HBMMIIHUSA-N

InChi: InChI=1S/C29H34Cl2FN3O3/c1-28(2,3)14-22-29(19-12-7-15(30)13-21(19)34-27(29)38)23(18-5-4-6-20(31)24(18)32)25(35-22)26(37)33-16-8-10-17(36)11-9-16/h4-7,12-13,16-17,22-23,25,35-36H,8-11,14H2,1-3H3,(H,33,37)(H,34,38)/t16-,17-,22-,23-,25+,29+/m0/s1

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO : ≥ 50 mg/mL (88.89 mM)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥360 days if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

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.

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