High Throughput Screening - A Bridge between Academy and Industry: from Idea to Drug

Modulation of biological processes through the action of small organic compounds is becoming increasingly attractive as a method of pathway interrogation. In contrast to transient or persistent genetic ablation by siRNA and shRNA, small molecules are “tunable” by dose, transferrable across species, and effective against redundant targets based upon structural homology. Further, an effective small molecule “probe” can be leveraged as a basis for drug optimization by medicinal chemistry. The Wohl Institute for Drug Discovery has established a small molecule screening facility in the G-INCPM with the goal of providing enabling technologies to the Israeli research community and promoting collaborations of outstanding biologists, clinicians, and chemists to facilitate probe discovery. Currently, the HTS unit maintains a compound library of ~100,000 molecules, including known drugs, natural products, peptides, diverse chemistry, and unique sets from academic and industrial collaborations. Using automated workstations, we miniaturize biochemical and cell-based assays to small volume format in 384-well and 1536-well plates and screen up to 16,000 compounds daily using plate-based technologies such as fluorescence intensity, luminescence, time-resolved FRET and Fluorescence Polarization or using automated microscopy for high-content image-based screening. Further, these technologies can be modified by assay development to enable screening of larger collections of RNAi or alternative platforms for validation of bioanalytes previously done by traditional ELISA or protein blots. Here, we present collaborations with basic research labs in the Weizmann Institute of Science which are the basis of ongoing chemical biology discovery projects.