Synonyms: (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
Molecular Formula: C29H34Cl2FN3O3
Molecular Weight: 562.5
Linear Structural Formula: C29H34Cl2FN3O3
MDL Number: MFCD28976052
Purity: >=98% (HPLC)
Storage: -20C
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 muM 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).