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    MI-773 (2'S,3R isomer, SAR-405838)
    MI-773 (2

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    This product is for research use only, not for human use. We do not sell to patients.
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    InvivoChem Cat #: V0021
    CAS #: 1303607-60-4Purity ≥98%

    Description: MI-773 (2'S,3R isomer, SAR405838) is a novel, potent, specific and orally bioavailable small molecule antagonist of MDM2/piro-oxindole HDM2 (Murine double minute 2/human double minute 2) with a Ki value of 0.88 nM. It has potential anticancer activity. 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). 

    Reference: Cancer Res. 2014 Oct 15;74(20):5855-65.

    Related CAS #: 1303607-60-4; 1303607-07-9; 

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    Molecular Weight (MW)562.50
    FormulaC29H34Cl2FN3O3
    CAS No.1303607-60-4
    Storage-20℃ for 3 years in powder form
    -80℃ for 2 years in solvent
    Solubility (In vitro)DMSO: 100 mg/mL (177.77 mM)
    Water:<1 mg/mL (slightly soluble or insoluble)
    Ethanol: 31 mg/mL warming (55.11 mM)
    Other infoInChi Key: IDKAKZRYYDCJDU-HBMMIIHUSA-N
    InChi Code: 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
    SMILES Code: O=C([[email protected]](N[[email protected]]1CC(C)(C)C)[[email protected]](C2=CC=CC(Cl)=C2F)[[email protected]@]31C(NC4=C3C=CC(Cl)=C4)=O)N[[email protected]]5CC[[email protected]](O)CC5
    Chemical Name/Synonyms(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; SAR-405838; SAR 405838; SAR405838; MI-773; MI773; MI 773


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    In VitroMI-773 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
    In VivoIn 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).
    Animal modelSCID mice with SJSA-1 osteosarcoma (females), acute lymphoblastic leukemia RS4;11 (females), LNCaP prostate cancer (males), or HCT-116 colon cancer (females) xenograft model
    Formulation & Dosages10% PEG400: 3% Cremophor: 87% PBS, or 2% TPGS: 98% PEG200; 200 mg/kg; Oral
    References[1] Wang S, et al. Cancer Res. 2014, 74(20), 5855-5865.


    These protocols are for reference only. InvivoChem does not independently validate these methods.

     

    MI-773 (SAR405838)


     

    MI-773 (SAR405838)

    Microsoft Word - NIHMS621402-manuscript-1SAR405838 potently activates p53 in the SJSA-1 and HCT-116 cancer cell lines and strongly induces PUMA up-regulation and cleavage of caspase-3 and PARP in the SJSA-1 cell line but not in the HCT-116 cell line. Wang S, et al. Cancer Res. 2014, 74(20), 5855-5865.


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