HSP (Heat shock proteins) are a group of proteins induced by heat shock, the most prominent members of this group are a class of functionally related proteins involved in the folding and unfolding of other proteins. HSPs are found in virtually all living organisms, from bacteria to humans. Especially, Hsp90 is one of the most common of the heat-related proteins. Hsp90 is a chaperone protein that assists other proteins to fold properly, stabilizes proteins against heat stress, and aids in protein degradation. Moreover, it also stabilizes a number of proteins required for tumor growth.

Geldanamycin, an ansamycin antitumor antibiotic, is an Hsp90 inhibitor with antimicrobial and antitumor activities. For example, Geldanamycin could inhibit many Gram-positive and some Gram-negative bacteria. In addition, Geldanamycin binds to the N-terminal ATP/ADP-binding domain of Hsp90, and also inhibits the inherent ATPase activity of Hsp90. Moreover, Geldanamycin shows potent antitumor activity in cell culture and animal models, and correlation between the downregulation of mutant p53, p185^erbB2, and Raf-1 and the antiproliferative activity of such compounds suggests that it act via Hsp90. Besides, Geldanamycin also has anti-viral and anti-inflammatory effects. Geldanamycin plays an important role in attenuating virus infection-induced acute lung injury (ALI) or acute respiratory distress syndrome (ARDS), by reducing the host’s inflammatory responses.

To sum up, Geldanamycin, an antitumor antibiotic, is an Hsp90 inhibitor with antimicrobial, antitumor, anti-viral and anti-inflammatory activities.

References:

[1] S M Roe, et al. J Med Chem. 1999 Jan 28;42(2):260-6.

[2] Chengmin Wang, et al. Front Cell Infect Microbiol. 2017 Jun 15;7:267.