CCT251236 is an orally available pirin ligand from a heat shock transcription factor 1 (hsf1) phenotypic screen with an IC 50 of 19 nM for inhibition of HSF1-mediated HSP72 induction.
In Vitro
CCT251236 (0-100 nM; 24hours) displays a desired balance of in vitro properties, while maintaining excellent cellular activity with a pIC50=7.73 ± 0.07 (IC 50 =19 nM) for inhibition of HSF1-mediated HSP72 induction. The free GI 50 is 1.1 nM in SK-OV-3 cells that calculated from the free fraction in the cell assay. CCT251236 (0-100 nM; 24 hours) blocks 17-AAG induced he HSF1-mediated heat-shock proteins, HSP72 and HSP27 expression as a concentration manner in SK-OV-3 cells. CCT251236 (0-100 nM; 24 hours), pre-treated with 250 nM 17-AAG for 6h, blocks the induction of HSPA1A mRNA by 17-AAG in a dosedependent manner. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Western Blot AnalysisCell Line: SK-OV-3 cells Concentration: 0 nM; 10 nM; 100 nM Incubation Time: 24 hours Result: Inhibited HSP72 and HSP27 expression at the dose of 10 nM. RT-PCRCell Line: SK-OV-3 cells Concentration: 0 nM; 10 nM; 100 nM and 1000 nM Incubation Time: 24 hours Result: Decreased HSPA1A mRNA level.
In Vivo
CCT251236 (oral adminstation; 5 or 20 mg/kg) in nontumor bearing immunocompetent BALB/c mice exhibits free C av 0-24h value of 2.0 nM and 1.2 nM, respectively. CCT251236 (oral adminstation; 20 mg/kg; 33 days) has a clear therapeutic efficacy in mice with a tumor growth inhibition (%TGI) of 70% based on final tumor volumes. After 33 days, the mean tumor weights decreases 64% when compares to control group. In addition, the compound’s basicity and high volume of distribution shows in tumor withtumor concentrations of CCT251236 as high as 940 nM. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: Athymic mice with SK-OV-3 cellsDosage: 20 mg/kg; 33 days Administration: Oral adminstation Result: Was efficacious in SK-OV-3 cell induced-tumor mice model.
IC50& Target:HSP72 19 nM (IC 50 , SK-OV-3 cells)
Associated Targets
HSF1Tchem Heat shock factor protein 1 4 Activities
