Rapid Discovery of SGR-1505 MALT1 Inhibitor Case Study

This case study documents the rapid discovery of SGR-1505, a novel and potent MALT1 inhibitor, achieved within a 10-month timeframe. The process involved the evaluation of 8.2 billion compounds using Schrödinger's digital chemistry platform, which integrates advanced computational techniques such as physics-based modeling and machine learning. The project aimed to identify a compound with favorable drug-like properties for treating relapsed or refractory B-cell malignancies. The team utilized a De Novo Design strategy, combining synthetic-aware large-scale enumeration and crowdsourced medicinal chemistry ideation, to identify multiple novel series of inhibitors. The study highlights the challenges faced in optimizing MALT1 inhibitors, particularly regarding permeability and solubility, while maintaining potency. Ultimately, SGR-1505 was synthesized, demonstrating a favorable safety profile and preliminary efficacy in ongoing Phase 1 clinical trials. The findings underscore the effectiveness of digital technologies in enhancing drug discovery workflows and achieving rapid candidate identification.