For research use only. Not for therapeutic Use.
MI-773（Cat No.:I001162）is a selective inhibitor of the protein MDM2 (Mouse Double Minute 2), which plays a critical role in regulating the tumor suppressor p53. MDM2 normally inhibits p53 by promoting its degradation, and by blocking MDM2, MI-773 aims to activate p53, leading to cell cycle arrest, apoptosis, or senescence in cancer cells. This compound is being investigated for its potential in treating various cancers, particularly those with p53 mutations or dysfunctions in the MDM2-p53 pathway. Preclinical studies suggest MI-773 could enhance the effectiveness of cancer therapies, but further clinical trials are needed to assess its safety and efficacy.
| Catalog Number | I001162 |
| CAS Number | 1303607-60-4 |
| Synonyms | SAR405838 |
| Molecular Formula | C₂₉H₃₄Cl₂FN₃O₃ |
| Purity | ≥95% |
| Target | Metabolic Enzyme/Protease |
| Solubility | 10 mM in DMSO |
| Storage | -20°C |
| IC50 | 0.88 nM (Ki) |
| IUPAC Name | (2'R,3R,3'S,5'S)-6-chloro-3'-(3-chloro-2-fluorophenyl)-5'-(2,2-dimethylpropyl)-N-(4-hydroxycyclohexyl)-2-oxospiro[1H-indole-3,4'-pyrrolidine]-2'-carboxamide |
| 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 |
| InChIKey | IDKAKZRYYDCJDU-AEPXTFJPSA-N |
| SMILES | CC(C)(C)C[C@H]1[C@@]2([C@H]([C@@H](N1)C(=O)NC3CCC(CC3)O)C4=C(C(=CC=C4)Cl)F)C5=C(C=C(C=C5)Cl)NC2=O |
| Reference | </br>1:A phase I study of SAR405838, a novel human double minute 2 (HDM2) antagonist, in patients with solid tumours. de Jonge M, de Weger VA, Dickson MA, Langenberg M, Le Cesne A, Wagner AJ, Hsu K, Zheng W, Macé S, Tuffal G, Thomas K, Schellens JH.Eur J Cancer. 2017 May;76:144-151. doi: 10.1016/j.ejca.2017.02.005. Epub 2017 Mar 17. PMID: 28324749 </br>2:Novel MDM2 inhibitor SAR405838 (MI-773) induces p53-mediated apoptosis in neuroblastoma. Lu J, Guan S, Zhao Y, Yu Y, Wang Y, Shi Y, Mao X, Yang KL, Sun W, Xu X, Yi JS, Yang T, Yang J, Nuchtern JG.Oncotarget. 2016 Dec 13;7(50):82757-82769. doi: 10.18632/oncotarget.12634. PMID: 27764791 Free PMC Article</br>3:TP53 mutations emerge with HDM2 inhibitor SAR405838 treatment in de-differentiated liposarcoma. Jung J, Lee JS, Dickson MA, Schwartz GK, Le Cesne A, Varga A, Bahleda R, Wagner AJ, Choy E, de Jonge MJ, Light M, Rowley S, Macé S, Watters J.Nat Commun. 2016 Aug 31;7:12609. doi: 10.1038/ncomms12609. PMID: 27576846 Free PMC Article</br>4:SAR405838: A Novel and Potent Inhibitor of the MDM2:p53 Axis for the Treatment of Dedifferentiated Liposarcoma. Bill KL, Garnett J, Meaux I, Ma X, Creighton CJ, Bolshakov S, Barriere C, Debussche L, Lazar AJ, Prudner BC, Casadei L, Braggio D, Lopez G, Zewdu A, Bid H, Lev D, Pollock RE.Clin Cancer Res. 2016 Mar 1;22(5):1150-60. doi: 10.1158/1078-0432.CCR-15-1522. Epub 2015 Oct 16. PMID: 26475335 Free PMC Article</br>5:Significant Differences in the Development of Acquired Resistance to the MDM2 Inhibitor SAR405838 between In Vitro and In Vivo Drug Treatment. Hoffman-Luca CG, Yang CY, Lu J, Ziazadeh D, McEachern D, Debussche L, Wang S.PLoS One. 2015 Jun 12;10(6):e0128807. doi: 10.1371/journal.pone.0128807. eCollection 2015. PMID: 26070072 Free PMC Article</br>6:SAR405838: an optimized inhibitor of MDM2-p53 interaction that induces complete and durable tumor regression. 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.Cancer Res. 2014 Oct 15;74(20):5855-65. doi: 10.1158/0008-5472.CAN-14-0799. Epub 2014 Aug 21. PMID: 25145672 Free PMC Article |
