RO8994

Cas No.:	1309684-94-3
Synonyms:	RO8994,RO-8994,RO 8994
SMILES:	C1=C(Cl)C=CC2[C@]3([C@H](C4=CC=CC(Cl)=C4F)[C@@H](C(=O)NC4=C(OC)C=C(C(=O)N)C=C4)N[C@@H]3CC(C)(C)C)C(=O)NC1=2
Formula:	C31H31Cl2FN4O4
M.Wt:	613.51
Purity:	>98%
Sotrage:	2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO

Description:	RO8994 is a highly potent and selective series of spiroindolinone small-molecule MDM2 inhibitor, with IC50 of 5 nM (HTRF binding assays) and 20 nM (MTT proliferation assays).
Target:	IC50 value: 5 nM (in HTRF binding assays), 20 nM (in MTT proliferation assays) Target: MDM2
In Vivo:	RO8994 displays remarkable tumor growth inhibition in the wild-type p53, MDM2-amplified SJSA-1 osteosarcoma tumor xenograft model - exhibiting significant (>60%) tumor growth inhibition at the low dose of 1.56 mg/kg, tumor stasis at 3.125 mg/kg and regression at 6.25 mg/kg.
In Vitro:	RO8994 represents a new generation of p53-MDM2 antagonists with marked improvement in pharmacological properties for potential clinical development. RO8994 induces dose-dependent up-regulation of p53 target genes and apoptosis in wild-type p53 cancer cells, consistent with its non-genotoxic mechanism of p53 activation.
References:	[1]. Zhang Z, et al. Discovery of potent and selective spiroindolinone MDM2 inhibitor, RO8994, for cancer therapy. Bioorg Med Chem. 2014 Aug 1;22(15):4001-4009.