HSP27: Inhibitors

Structure of Thiolutin, an HSP27 inhibitor
Structure of Thiolutin, an Hsp27 perturbing agent
Due to its anti-apoptotic effects and the cytoprotection against chemotherapeutic drugs, Hsp27 has been proposed as a therapeutic target for over 20 years and this is supported by the publication of more recent reviews97,98. Thus, Hsp27 modulators can decrease the protective function of the protein in cell apoptotic regulation99,100,101. These agents exhibit promising antitumor activities in preclinical models of a variety of tumors expressing high levels of Hsp27 and may have significant clinical potential102,103. So far, the most effective strategy to target Hsp27 is antisense oligonucleotides (ASO) or siRNA,90 which can decrease Hsp27 expression in in vitro cell culture and in vivo xenograft as well101,104. The fourth generation ASO of Hsp27, OGX-427102, has shown clinical evidence of antitumor activity despite the limitations associated with ASO administration. The results emphasizes that Hsp27 is a good oncotherapeutic target. Small molecule Hsp27 modulators without the administration problems are highly possible to show even better clinical outcome.