Geldanamycin as a Potential Anti-Cancer Agent: Its Molecular Target and Biochemical Activity

Abstract

Heat shock protein 90 is one of the most abundantcellularproteins. Although its functions are still being characterized,itappears to serve as a chaperone for a growing list of cellsignaling proteins, including many tyrosine and serine/threoninekinases, involved in proliferation and/or survival. Thebenzoquinone ansamycin geldanamycin has been shown to bind toHsp90and to specifically inhibit this chaperone's function, resultinginclient protein destabilization. Its ability to simultaneouslystimulate depletion of multiple oncogenic proteins suggests thatgeldanamycin, or other molecules capable of targeting Hsp90 incancer cells, may be of clinical benefit.