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CCT251236

CAS No. : 1693731-40-6

產(chǎn)品活性：CCT251236 is an orally available pirin ligand from a heat shock transcription factor 1 (hsf1) phenotypic screen with an IC₅₀ of 19 nM for inhibition of HSF1-mediated HSP72 induction.

研究領(lǐng)域：Cell Cycle/DNA Damage  |  Metabolic Enzyme/Protease

作用靶點：HSP

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 (IC₅₀=19 nM) for inhibition of HSF1-mediated HSP72 induction. The free GI₅₀?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.

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.

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