MI-773 (SAR405838)

Name: MI-773 (SAR405838)
Brand: Selleck Chemicals
SKU: S7649
Rating: 5 (5 reviews)

For research use only.

Catalog No.S7649

5 publications

Molecular Weight(MW): 562.50

MI-773 (SAR405838) is an orally available MDM2 antagonist with K_i of 0.88 nM. Phase 1.

Selleck's MI-773 (SAR405838) has been cited by 5 publications

Cancers (Basel), 2020, 12(8):E2157

PubMed: 32759684 ( click the link to review the publication )

EMBO J, 2019, 38(20):e102096

PubMed: 31483066 ( click the link to review the publication )

Cell Chem Biol, 2018, 25(6):761-774

PubMed: 29681526 ( click the link to review the publication )

Oncotarget, 2017, 8(26):43008-43022

PubMed: 28498808 ( click the link to review the publication )

Oncotarget, 2016, 7(50):82757-82769

PubMed: 27764791 ( click the link to review the publication )

1 Customer Review

A panel of four NB cell lines were seeded in six-well plates with indicated concentrations of SAR405838 and agar, and grown for 2 to 3 weeks. Cells were stained with crystal violet for 4 hours. Colonies were counted and colony numbers were represented as % vehicle ± S.D. with P < 0.05 (*), P < 0.01 (**) or P < 0.001 (***) (Student's t-test, two-tailed) as indicated.

Oncotarget, 2016, 7(50):82757-82769. MI-773 (SAR405838) purchased from Selleck.

Purity & Quality Control

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Biological Activity

Description

MI-773 (SAR405838) is an orally available MDM2 antagonist with K_i of 0.88 nM. Phase 1.

Targets

p53 ^[1]	MDM2 ^[1] (Cell-free assay)
	0.88 nM(Ki)

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]

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]

Protocol

Kinase Assay:^[1]	- Collapse 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:^[1]	- Collapse 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. (Only for Reference)
Animal Research: ^[1]	- Collapse 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. (Only for Reference)

References

[1] Wang S, et al. Cancer Res. 2014, 74(20), 5855-5865.

Solubility (25°C)

In vitro	DMSO	100 mg/mL (177.77 mM)
	Ethanol	31 mg/mL warmed (55.11 mM)
	Water	Insoluble

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight	562.50
Formula	C₂₉H₃₄Cl₂FN₃O₃
CAS No.	1303607-60-4
Storage	3 years-20°C powder 2 years-80°C in solvent
Synonyms	N/A
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

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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 DMSO master liquid, next addμL PEG300， mix and clarify, next addμL Tween 80，mix and clarify, next add μL ddH₂O，mix and clarify.

Note：1.Please make sure the liquid is clear before adding the next solvent.
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Clinical Trial Information (data from https://clinicaltrials.gov, updated on 2020-09-01)

NCT Number	Recruitment	interventions	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT01985191	Completed	Drug: SAR405838\|Drug: Pimasertib	Neoplasm Malignant	Sanofi\|Merck KGaA Darmstadt Germany	November 2013	Phase 1
NCT01636479	Completed	Drug: SAR405838	Neoplasm Malignant	Sanofi	July 13 2012	Phase 1

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

Tel: +1-832-582-8158 Ext:3

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MI-773 (SAR405838)