WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 206069
Description: MI-773, also known as SAR405838, is an orally available spiro-oxindole HDM2 (human double minute 2) antagonist with potential antineoplastic activity. Upon oral administration, the p53-HDM2 protein-protein interaction inhibitor MI-773 binds to HDM2, preventing the binding of the HDM2 protein to the transcriptional activation domain of the tumor suppressor protein p53. By preventing this HDM2-p53 interaction, the proteosome-mediated enzymatic degradation of p53 is inhibited and the transcriptional activity of p53 is restored, which may result in the restoration of p53 signaling and lead to the p53-mediated induction of tumor cell apoptosis. HDM2, a zinc finger protein and a negative regulator of the p53 pathway, is often overexpressed in cancer cells. It has been implicated in cancer cell proliferation and survival. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus)
MedKoo Cat#: 206069
Name: MI-773 (SAR-405838)
Chemical Formula: C29H34Cl2FN3O3
Exact Mass: 561.19613
Molecular Weight: 562.51
Elemental Analysis: C, 61.92; H, 6.09; Cl, 12.60; F, 3.38; N, 7.47; O, 8.53
Synonym: SAR-405838; SAR 405838; SAR405838; MI-773; MI773; MI 773
IUPAC/Chemical Name: (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
SMILES Code: 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
1: Hoffman-Luca CG, Yang CY, Lu J, Ziazadeh D, McEachern D, Debussche L, Wang S.
1. Significant Differences in the Development of Acquired Resistance to the MDM2
Inhibitor SAR405838 between In Vitro and In Vivo Drug Treatment. PLoS One. 2015
Jun 12;10(6):e0128807. doi: 10.1371/journal.pone.0128807. eCollection 2015.
PubMed PMID: 26070072; PubMed Central PMCID: PMC4466389.
2: Hoffman-Luca CG, Ziazadeh D, McEachern D, Zhao Y, Sun W, Debussche L, Wang S.
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):2558-68. doi:
10.1158/1078-0432.CCR-14-2506. Epub 2015 Mar 9. PubMed PMID: 25754349.
3: Wang S, Sun W, Zhao Y, McEachern D, Meaux I, Barrière C, Stuckey JA, Meagher
JL, Bai L, Liu L, Hoffman-Luca CG, Lu J, Shangary S, Yu S, Bernard D, Aguilar A,
Dos-Santos O, Besret L, Guerif S, Pannier P, Gorge-Bernat D, Debussche L.
SAR405838: an optimized inhibitor of MDM2-p53 interaction that induces complete
and durable tumor regression. Cancer Res. 2014 Oct 15;74(20):5855-65. doi:
10.1158/0008-5472.CAN-14-0799. Epub 2014 Aug 21. PubMed PMID: 25145672; PubMed
Central PMCID: PMC4247201.