KRIBB11

Description: KRIBB11, a novel and potent inhibitor of Heat shock factor 1 (HSF1), abolishes the heat shock-induced luciferase activity with an IC50 of 1.2 uM. Heat shock protein 90 (Hsp90) is the master switch for heat shock protein (HSP) expression in eukaryotes and has an important role in many cancers. Biochemical inhibitors of Hsp90 are in advanced clinical development for the treatment of solid and hematological malignancies. As an inhibitor of the transcription factor Heat Shock Factor 1 (HSF1), KRIBB11 can inhibit cancer cell proliferation, arrests the cell cycle at G2/M phase and induces apoptosis. But it does not inhibit heat shock-induced recruitment of HSF1 to the hsp70 promoter or phosphorylation of HSF1 Ser-230. KRIBB11 inhibits heat shock-induced recruitment of pTEFb to the hsp70 promoter and p-TEFb-dependent Phosphorylation of polII CTD Ser-2. Immunoblotting assays showed that the expression of HSP70 was lower in KRIBB11-treated tumor tissue than in control tissues. Because HSPs are expressed at high levels in a wide range of tumors, these results strengthen the rationale for targeting HSF1 in cancer therapy.

References: J Biol Chem. 2011 Jan 21; 286(3):1737-47