Home Apoptosis MDM2/MDMX antagonist - p53 activator SAR405838 For research use only.

SAR405838

Synonyms: MI-77301, MI-773

SAR405838 is an orally available MDM2 antagonist with Ki of 0.88 nM. SAR405838 (CAS: 1303607-60-4) is a diastereomer of MI-773 (CAS: 1303607-07-9). Phase 1.

SAR405838 Chemical Structure

SAR405838 Chemical Structure

CAS No. 1303607-60-4

Purity & Quality Control

SAR405838 Related Products

Signaling Pathway

MDM2/MDMX Signaling Pathways

MDM2/MDMX Signaling Pathway

Biological Activity

Description SAR405838 is an orally available MDM2 antagonist with Ki of 0.88 nM. SAR405838 (CAS: 1303607-60-4) is a diastereomer of MI-773 (CAS: 1303607-07-9). Phase 1.
Targets
MDM2 [1]
(Cell-free assay)		 MDM2 [1]
0.88 nM(Ki) 8.2 nM(Kd)
In vitro
In vitro MI-773 binds to MDM2 with Ki of 0.88 nM. MI-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. [1]
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 MI-773 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.
Cell Research Cell lines SJSA-1, RS4;11, LNCaP, SAOS-2, PC-3, SW620, HCT-116, and HCT-116 (p53-/-) cells
Concentrations 100 μM
Incubation Time ~48 h
Method Cell growth inhibition activity is determined in a water-soluble tetrazolium-based assay. Cell death is measured by trypan blue staining and apoptosis is determined using an Annexin V-FLUOS staining kit.
In Vivo
In vivo In 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,). [1]
Animal Research Animal Models SCID mice with SJSA-1 osteosarcoma (females), acute lymphoblastic leukemia RS4;11 (females), LNCaP prostate cancer (males), or HCT-116 colon cancer (females) xenograft model
Dosages 200 mg/kg
Administration p.o.
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

Chemical Information & Solubility

Molecular Weight 562.50 Formula

C29H34Cl2FN3O3
CAS No. 1303607-60-4 SDF --
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
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 100 mg/mL ( (177.77 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh 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.

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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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