Supply problems associated with GA derivatives and
radicicol, together with GA toxicity problems, led Chiosis
et al. to propose use of a simple substituted adenine derivative
as a potential base molecule. Significantly, the proposal was
based on considering which particular substructures might
provide ATP-mimics with improved binding characteristics,
rather than on computerized modeling. Thus, knowledge of
the requirements of the ATP-binding pocket of Hsp90, and
demonstration that a small molecule could function as a
cytostatic agent, provided the intellectual stimulus for
designing the purine-based PU class of compounds