Home Apoptosis MDM2/MDMX antagonist SAR405838

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SAR405838 MDM2/MDMX antagonist

Cat.No.S7649

SAR405838 is an orally available MDM2 antagonist with Ki of 0.88 nM. This compound is a diastereomer of MI-773 (CAS: 1303607-07-9). Phase 1.
SAR405838 MDM2/MDMX antagonist Chemical Structure

Chemical Structure

Molecular Weight: 562.50

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Quality Control

Batch: Purity: 99.68%
99.68

Solubility

In vitro
Batch:

DMSO : 100 mg/mL (177.77 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Ethanol : 31 mg/mL

Water : Insoluble

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In vivo
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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
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Chemical Information, Storage & Stability

Molecular Weight 562.50 Formula

C29H34Cl2FN3O3

 Storage (From the date of receipt)
CAS No. 1303607-60-4 -- Storage of Stock Solutions

Synonyms MI-77301, MI-773 Smiles CC(C)(C)CC1C2(C(C(N1)C(=O)NC3CCC(CC3)O)C4=C(C(=CC=C4)Cl)F)C5=C(C=C(C=C5)Cl)NC2=O

Mechanism of Action

Targets/IC50/Ki
MDM2
(Cell-free assay)
0.88 nM(Ki)
MDM2
8.2 nM(Kd)
In vitro
MI-773 binds to MDM2 with Ki of 0.88 nM. This compound 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.
Kinase Assay
Fluorescence-polarization binding assay
Binding affinities of MDM2 inhibitors and p53 peptide to MDM2 protein are determined using an Fluorescence-polarization (FP) binding assay. Binding affinities of this compound to Bcl-2, Bcl-xL, Mcl-1, and β-catenin are determined using a competitive FP-based assay, and its binding affinity to MDMx is determined using Biolayer Interferometry technology.
In vivo
In the SJSA-1 osteosarcoma, acute lymphoblastic leukemia RS4;11, LNCaP prostate cancer, and HCT-116 colon cancer xenograft model, this compound (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,).
References

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT01985191 Completed
Neoplasm Malignant
Sanofi|Merck KGaA Darmstadt Germany
 November 2013 Phase 1
NCT01636479 Completed
Neoplasm Malignant
Sanofi
 July 13 2012 Phase 1

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