1303607-60-4MI-773 (SAR405838)

产品属性：

Cas No.1303607-60-4

别名

化学名 (2'S,3R,4'S,5'R)-6-chloro-4'-(3-chloro-2-fluorophenyl)-N-((1r,4R)-4-hydroxycyclohexyl)-2'-neopentyl-2-oxospiro[indoline-3,3'-pyrrolidine]-5'-carboxamide

分子式 C29H34Cl2FN3O3

分子量 562.5

溶解度 ≥ 17.2mg/mL in DMSO

储存条件 Store at -20°C
General tips  For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.
Shipping Condition     Evaluation sample solution : ship with blue ice
All other available size: ship with RT , or blue ice upon request
产品描述：
MI-773 (SAR405838) is a specific antagonist of MDM2 with Ki value of 0.88 nM [1].

Murine double minute 2 (MDM2) is a primary negative regulator of wild-type p53, which is a tumor suppressor. MDM2 is an E3 ubiquitin ligase that induces p53 degradation and blocks the p53 trans-activation domain (TAD) [1].

MI-773 (SAR405838) is a MDM2 antagonist. MI-773 (SAR405838) inhibited cells growth in SJSA-1, RS4;11, LNCaP and HCT-116 cancer cell lines with IC50 values of 0.092, 0.089, 0.27 and 0.20 μM, respectively. MI-773 (SAR405838) exhibited high selectivity over cancer cell lines with mutated or deleted p53 with IC50 values of >20, >10, >10 and >10 μM for HCT-116 (p53-/-), SAOS-2, PC-3 and SW620 cancer cell lines, respectively [1].

In mice bearing the SJSA-1, HCT-116, RS4;11, and LNCaP xenograft tumors, MI-773 (SAR405838) increased the levels of MDM2, p21 and p53 proteins in a dose- and time-dependent way and induced apoptosis. In the SJSA-1 xenograft model, MI-773 (SAR405838) (30-100 mg/kg) induced tumor regression and significantly inhibited tumor growth [1].

Reference:

[1].  Wang S, Sun W, Zhao Y, et al. SAR405838: an optimized inhibitor of MDM2-p53 interaction that induces complete and durable tumor regression. Cancer Res, 2014, 74(20): 5855-5865.