ATPase inhibitors of heat-shock protein 90 second season

In the past four years, the ATP-dependent heat-shock protein 90 has remained the focus of much interest. Phase I and phase II anticancer clinical trials with first-generation inhibitors, although sometimes disappointing, have yet to report a forbidding side-effect inherent to the inhibition of this chaperone, which has a very complex and widespread role in cell biochemistry. Research in the field has started to unravel an elaborate regulation picture leading to the proper folding of many proteins. On the medicinal chemistry side, a second wave of inhibitors has been reported. This review attempts to describe all the ATPase inhibitors of HSP90 reported since our last survey.