The Discovery of BIIB021 and BIIB028
This chapter describes the fundamental ideas that led to the discovery of the purine-based Hsp90 inhibitors BIIB021 and BIIB028. The first-generation drug BIIB021 completely inhibits tumor growth in murine cancer models when administered orally at its maximum tolerated dose (MTD, 625 mg/kg/week, p.o.). BIIB021 is the first Hsp90 inhibitor to have entered clinical trials as an oral drug, and completed Phase II clinical trials. The second-generation compound, BIIB028, is a highly water-soluble molecule designed for parenteral administration. BIIB028 is a phosphate pro-drug that releases the active metabolite CF2772