Abstract
AbstractDrug discovery’s rising costs and complexities require innovative strategies to identify viable therapeutic targets. We developed a computational pipeline to pinpoint protein targets lacking known small molecule probes, focusing on sites traditionally considered challenging for small molecule intervention but validated by FDA-approved biologics. Our approach, which integrates machine learning, public databases, and structural analysis, targeted autoimmune diseases. This method identified IL12B as a promising candidate, uncovering a potential small molecule binding site involved in dimer formation. Inhibitors targeting this site could offer benefits such as shorter half-lives and more precise tissue distribution compared to existing biologics. These findings present a new opportunity to develop small molecule therapeutics for IL12B, potentially improving the safety and efficacy of treatments for conditions like inflammatory bowel disease (IBD).
Publisher
Cold Spring Harbor Laboratory
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