RO8994 Chemical Properties

Boiling point:

753.5±60.0 °C(Predicted)

Density 

1.41±0.1 g/cm3(Predicted)

storage temp. 

Store at -20°C

solubility 

DMF:12.5(Max Conc. mg/mL);20.4(Max Conc. mM)
DMSO:14.0(Max Conc. mg/mL);22.8(Max Conc. mM)
Ethanol:5.0(Max Conc. mg/mL);8.1(Max Conc. mM)

form 

A crystalline solid

pka

12.00±0.70(Predicted)

color 

White to off-white

InChIKey

MURAVORBGFDSMA-ISKXDESKSA-N

SMILES

N1C2=C(C=CC(Cl)=C2)[C@@]2([C@@H](C3=CC=CC(Cl)=C3F)[C@H](C(NC3=CC=C(C(N)=O)C=C3OC)=O)N[C@H]2CC(C)(C)C)C1=O

RO8994 Usage And Synthesis

Description

RO8994 is an inhibitor of the protein-protein interaction between MDM2 and the tumor suppressor p53 in a homogeneous time-resolved fluorescence (HTRF) binding assay (IC₅₀ = 5 nM). It inhibits the proliferation of SJSA-1, RKO, and HCT116 cells with an average IC₅₀ value of 20 nM and increases apoptosis in SJSA-1 cells in a concentration-dependent manner. RO8994 reduces tumor growth and induces tumor regression in an SJSA-1 osteosarcoma mouse xenograft model when administered at doses of 1.56 and 6.25 mg/kg, respectively.

Uses

RO 8994 is a potent and selective spiroindolinone MDM2 inhibitor, and potential useful for cancer therapy.

References

[1] ZHUMING ZHANG . Discovery of potent and selective spiroindolinone MDM2 inhibitor, RO8994, for cancer therapy[J]. Bioorganic & Medicinal Chemistry, 2014, 22 15: Pages 4001-4009. DOI: 10.1016/j.bmc.2014.05.072