Anti-HSP90 monoclonal antibody, clone BD99

Introduction Heat shock protein 90 (Hsp90) is one of the most critical chaperones amenable to mediating the folding and maturation of more than 300 client proteins. In normal cells, Hsp90 chaperone cycle is required for regulating multiple cellular processes to maintain homeostasis. However, extremely overexpressed Hsp90 in neoplastic cells results in the dysregulation of client proteins, many of which are indispensable to the accumulation of cancer hallmarks, such as infinite proliferation and increased invasiveness. Consequently, modulation of Hsp90 activity has been considered as a potential strategy for cancer treatment. Areas covered This review recapitulated recent patents' progress in the development of Hsp90 inhibitors with potent antitumor activities during 2013 to present. Besides, the structural-activity relationships of the patented inhibitors and their structural similarity were also discussed. Expert opinion Hsp90, as an anticancer target, has been investigated for several decades. The first generation of Hsp90 inhibitors exhibited potent antitumor activities in preclinical trials but were trapped in different phases of clinical trials. The second generation of Hsp90 inhibitors has been identified with increased specificity and security through structure modification. Moreover, these inhibitors may offer opportunities for studies of Hsp90 chaperone and development of Hsp90 inhibition therapy.

Stimulator of interferon genes (STING) plays important roles in the DNA-mediated innate immune responses. However, the regulatory mechanism of STING in terms of stabilization is not fully understood. Here, we identified the chaperone protein Hsp90s as novel STING interacting proteins. Treatment with an Hsp90 inhibitor 17-AAG and knockdown of Hsp90 beta but not Hsp90 alpha reduced STING at protein level, resulted in the suppression of IFN induction in response to stimulation with cGAMP, and infections with HSV-1 and Listeria monocytogenes. Collectively, our results suggest that the control of STING protein by Hsp90 beta is a critical biological process in the DNA sensing pathways.