Rational design of ZAP70 and HSP90 inhibitors

Abstract

Several virtual screening techniques are currently available to rapidly screen compounds from virtual compound databases. In virtual screening, computational models are used to predict the biological activity of compounds. The computational models can be generated and validated utilizing either the 3D structure of the target or a set of active analogues specific to the target. Computational models can also be built combining information from structure of the drug target and a set of active analogues specific to the target. Utilizing these technologies to discover small-molecule ZAP70 and HSP90 inhibitors, we employed consensus models generated by combining both structure-based and active analogue-based methods. In this study, we present the pharmacophore modeling, the docking studies, and finally the use of the consensus models to discover a set of novel ZAP70 and HSP90 inhibitors with biological activity in HSP90-overexpressing SKBR3 cells.