CCT251236 is an orally available Pirin ligand obtained from a heat shock transcription factor 1 (hsf1) phenotypic screen. It inhibits HSF1-mediated HSP72 induction (IC50: 19 nM).

CCT367766 (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. CCT367766 blocks the induction of HSPA1A mRNA by 17-AAG in a dose-dependent manner. CCT367766 (0-100 nM; 24hours) displays the 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. CCT367766 (0-100 nM; 24 hours) pre-treated with 250 nM 17-AAG for 6h.

CCT367766 (p.o.; 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 decrease 64% when compares to the control group. In addition, the compound's basicity and the high volume of the distribution shown in tumors with tumor concentrations of?CCT367766?as high as 940 nM. CCT367766 (p.o.; 5 or 20 mg/kg) in nontumor bearing immunocompetent BALB/c mice exhibits free?Cav0–24h?value of 2.0 nM and 1.2 nM, respectively [2].

1693731-40-6

C32H32N4O5

552.62

DMSO:150 mg/mL (271.43 mM)
Powder: -20°C for 3 years
In solvent: -80°C for 2 years