ABSTRACT
The discovery of the ability of geldanamycin (GM, 1; Figure 18.1)1 to inhibit the chaperone protein, Hsp90,2 and thus cause death of cancer cells has caused an extraordinary interest in the benzoquinone ansamycins (BAs) as candidates for drug development. At the time of this œrst review,3 there were only two candidates in clinical trials, 17-allylamino-17-demethoxygeldanamycin (17-AAG, 2; Figure 18.1) and 17-dimethylamino-17-demethoxygeldanamycin (17-DMAG, 3; Figure 18.1). In the following six years, there have been hundreds of modiœed products prepared and tested, and the promise of potential broad spectrum activity against cancer still looks promising, although no candidate has been unblemished in clinical testing yet. The abundance of new research has also stimulated several excellent reviews that describe not only the BAs,4,5 but also the intense study done on heat shock protein 90 (Hsp90), its role in both normal and malignant cells, and its impact on the search for other molecules with Hsp90-inhibition activity.6
