Ansamycin Class of Natural Product Hsp90 Inhibitors

Synonyms

Benzoquinone ansamycin; Geldanamycin; GM

Definition

Ansamycins are a family of antibiotics with antitumor activity. These include geldanamycin (GM), herbimycin A, and the macbecins, all of which contain benzoquinone structures. These antibiotics induce tumor cell death via inhibition of the heat shock protein 90 (Hsp90) chaperone complex and induce the degradation of key client proteins that are required for tumor survival.

Characteristics

Ansamycins, especially benzoquinone ansamycins, such as herbimycin and geldanamycin, were the first natural product Hsp90 inhibitors identified. Both molecules contain a benzoquinone moiety, which distinguishes them from other ansamycins and confers selectivity for Hsp90 inhibition. Since discovery, these molecules have been widely explored due to their broad-spectrum antitumor activity.

Benzoquinone ansamycins were initially discovered as naturally occurring antibiotics in the fermentation broth of Streptomyces hygroscopicusin 1970, with...