Methods of inhibiting the Hsp90 chaperone pathway including contacting one or more target cells with an effective amount of a naturally occurring beauvericin, a synthetic beauvericin, or a derivative, analog or prodrug, or a pharmacologically active salt thereof to reduce, decrease, or inhibit the Hsp90 chaperone pathway in the cells compared to a control are disclosed. The methods can reduce the viability of the target cells, for example, by increasing apoptosis or pro-apoptotic pathways. In preferred embodiments, the methods reduce or do not increase Hsp70, Hsp24, Hsp40, or HOP expression reduce or do not increase the heat shock response reduce or do not increase pro-survival pathways in the cells. Methods of treating diseases such as cancer, inflammatory diseases or disorders, neurodegenerative diseases, and infectious diseases using the disclosed compositions and methods are also disclosed.
