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SML2772

Sigma-Aldrich

SAR405838

≥98% (HPLC)

Synonym(s):

(2′S,3R,4′S,5′R)-6-Chloro-4′-(3-chloro-2-fluorophenyl)-2′-(2,2-dimethylpropyl)-1,2-dihydro-N-(trans-4-hydroxycyclohexyl)-2-oxospiro[3H-indole-3,3′-pyrrolidine]-5′-carboxamide, MI 77301, MI-77301, MI77301

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About This Item

Empirical Formula (Hill Notation):
C29H34Cl2FN3O3
CAS Number:
1303607-60-4
Molecular Weight:
562.50
MDL number:
MFCD28976052
UNSPSC Code:
12352200
NACRES:
NA.77

Quality Level

100

assay

≥98% (HPLC)

storage condition

desiccated

color

white to beige

solubility

DMSO: 2 mg/mL, clear

storage temp.

−20°C

SMILES string

O=C([C@@H]1N[C@@H](CC(C)(C)C)[C@@]2(C(NC3=C2C=CC(Cl)=C3)=O)[C@H]1C4=CC=CC(Cl)=C4F)N[C@@H]5CC[C@H](CC5)O

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

InChI key

IDKAKZRYYDCJDU-HBMMIIHUSA-N

Biochem/physiol Actions

SAR405838 (MI-77301) is an orally available (F = 67%/mouse, 48%/rat; 10 mg/kg p.o.), highly potent and selective Mdm2 (Hdm2) inhibitor (human Mdm2 Ki = 0.88 nM; no binding at 10 μM to Bcl-2, Bcl-xL, Mcl-1, Mdmx; no inhibition against >200 receptors/enzymes) that upregulates wild-type p53 activity (EC50 = 300-600 nM; SJSA-1) by blocking Mdm2-p53 interaction and Mdm2-mediated p53 degradation with 5-10-times higher potency than MI-219 and nutlin-3a. SAR405838 inhibits cancer growth in a wild-type p53-dependent manner both in cultures (IC50 = 89 nM/RS4;11, 92 nM/SJSA-1, 200 nM/HCT-116, 270 nM/LANCaP) and in xenograft models in vivo (50-200 mg/kg single or daily p.o. dosing).

wgk_germany

WGK 3

flash_point_f

Not applicable

flash_point_c

Not applicable

Certificates of Analysis (COA)

Search for Certificates of Analysis (COA) by entering the products Lot/Batch Number. Lot and Batch Numbers can be found on a product’s label following the words ‘Lot’ or ‘Batch’.

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A N Hata et al.
Oncogene, 36(47), 6581-6591 (2017-08-08)
There are currently no effective targeted therapies for KRAS mutant cancers. Therapeutic strategies that combine MEK inhibitors with agents that target apoptotic pathways may be a promising therapeutic approach. We investigated combining MEK and MDM2 inhibitors as a potential treatment
Maja de Jonge et al.
European journal of cancer (Oxford, England : 1990), 76, 144-151 (2017-03-23)
In tumours with wild-type TP53, the tumour-suppressive function of p53 is frequently inhibited by HDM2. This phase I, dose-escalating study investigated the maximum tolerated dose (MTD), safety, pharmacokinetics and pharmacodynamics of SAR405838, an HDM2 inhibitor, in patients with advanced solid tumours (NCT01636479).
Sana AlQarni et al.
Oncogene, 37(29), 3998-4012 (2018-04-25)
Epstein-Barr virus (EBV)-associated Burkitt's lymphoma is characterised by the deregulation of c-Myc expression and a restricted viral gene expression pattern in which the EBV nuclear antigen-1 (EBNA1) is the only viral protein to be consistently expressed. EBNA1 is required for
Liye He et al.
Cancer research, 78(9), 2407-2418 (2018-02-28)
The molecular pathways that drive cancer progression and treatment resistance are highly redundant and variable between individual patients with the same cancer type. To tackle this complex rewiring of pathway cross-talk, personalized combination treatments targeting multiple cancer growth and survival
C Gianna Hoffman-Luca et al.
PloS one, 10(6), e0128807-e0128807 (2015-06-13)
SAR405838 is a potent and specific MDM2 inhibitor currently being evaluated in Phase I clinical trials for the treatment of human cancer. Using the SJSA-1 osteosarcoma cell line which harbors an amplified MDM2 gene and wild-type p53, we have investigated
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