1309684-94-3

1309684-94-3 structure

Name: RO8994
Chemical Name: ro8994
CAS Number: 1309684-94-3
Molecular Formula: C₃₁H₃₁Cl₂FN₄O₄
Molecular Weight: 613.50700
Catalog: Signaling Pathways Apoptosis MDM-2/p53
Create Date: 2016-02-15 06:50:51
Modify Date: 2024-01-07 18:05:09
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).IC50 value: 5 nM (in HTRF binding assays), 20 nM (in MTT proliferation assays)Target: MDM2in 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.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.

Name	ro8994
Synonyms	(2'S,3R,4'R,5'R)-N-(4-carbamoyl-2-methoxyphenyl)-6-chloro-4'-(3-chloro-2-fluorophenyl)-2'-neopentyl-2-oxospiro[indoline-3,3'-pyrrolidine]-5'-carboxamide Spiro[3H-indole-3,3'-pyrrolidine]-5'-carboxamide, N-[4-(aminocarbonyl)-2-methoxyphenyl]-6-chloro-4'-(3-chloro-2-fluorophenyl)-2'-(2,2-dimethylpropyl)-1,2-dihydro-2-oxo-, (2'S,3R,4'R,5'R)- RO 8994 RO-8994

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).IC50 value: 5 nM (in HTRF binding assays), 20 nM (in MTT proliferation assays)Target: MDM2in 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.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.
Related Catalog	Signaling Pathways >> Apoptosis >> MDM-2/p53 Research Areas >> Cancer
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.