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.
IC50&Target
HSP72
19 nM (IC50, SK-OV-3 cells)
体外研究
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.
Western Blot Analysis
Cell 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-PCR
Cell Line:
SK-OV-3 cells
Concentration:
0 nM; 10 nM; 100 nM and 1000 nM
Incubation Time:
24 hours
Result:
Decreased HSPA1A mRNA level.
体内研究
CCT251236 (oral adminstation; 5 or 20 mg/kg) in nontumor bearing immunocompetent BALB/c mice exhibits free Cav 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.
Animal Model:
Athymic mice with SK-OV-3 cells
Dosage:
20 mg/kg; 33 days
Administration:
Oral adminstation
Result:
Was efficacious in SK-OV-3 cell induced-tumor mice model.
分子式
C32H32N4O5
分子量
552.62
CAS号
1693731-40-6
运输条件
Room temperature in continental US; may vary elsewhere.