Idasanutlin Inhibitor

POWDER

99.55%

0-4°C for short term (days to weeks), or -20°C for long term (months).

616.48

1229705-06-9

C31H29Cl2F2N3O4

Consistent with structure.

Consistent with structure.

The test result is consistent with structure

Idasanutlin inhibits cell proliferation with IC50 of 30 nM, and induces dose-dependent p53 stabilization, cell cycle arrest, as well as cell apoptosis in cancer cells expressing wild-type p53.

In a mouse SJSA human osteosarcoma xenograft model, Idasanutlin (25 mg/kg p.o.) causes tumor growth inhibition and regression. In a SJSA xenograft model, Idasanutlin results in induction of apoptosis and antiproliferation.

Biochemical Binding Affinity – HTRF Assay: The p53-MDM2 HTRF assay is performed in buffer containing 50 mM Tris-HCl, pH 7.4, 100 mM NaCl, 1 mM DTT, 0.02 or 0.2 mg/ml BSA. Small-molecule inhibitors are stored in aliquots as 10 mM stock solutions in DMSO at 4°C in 96-deep-well plates. It is thawed and mixed immediately prior to testing. The compound is incubated with GST-MDM2 and a biotinylated p53 peptide for one hour at 37°C. Phycolink goat anti-GST (Type 1) allophycocyanin and Eu-8044-streptavidin are then added and followed by one hour incubation at room temperature. Plates are read using the Envision fluorescence reader. IC50 values are determined from inter-plate duplicate or triplicate sets of data. Data are analyzed by XLfit4 (Microsoft) using a 4 Parameter Logistic Model (Sigmoidal Dose-Response Model) and the equation Y= (A+ ((B-A)/ (1+((C/x)^D)))), where A and B are enzyme activity in the absence or presence of infinite inhibitor compound, respectively, C is the IC50 and D is the Hill coefficient.

Cell proliferation is evaluated by the tetrazolium dye assay. The concentration at which 50% inhibition (IC50) or 90% inhibition (IC90) of cell proliferation is determined from the linear regression of a plot of the logarithm of the concentration versus percent inhibition. (Only for Reference) Cell lines? wt-p53 cancer cell lines (SJSA1, RKO, HCT116)

Animal Model?Mice bearing SJSA human osteosarcoma xenografts

DMSO: 93 mg/mL (150.9 mM)
Ethanol: 8 mg/mL (12.97 mM)
Water: <1 mg/mL
(< 1 mg/ml refers to the product slightly soluble or insoluble)

Molecules; Mdm2; Mdm2 inhibitor