Our RORγ Library comprises 13,000 compounds.
RORγ, a nuclear receptor, is a promising target for autoimmune therapeutics due to its pivotal role as a master regulator of Th17 cell development. Th17 cells are implicated in autoimmune diseases, and RORγ plays a central role in their differentiation and function. Inhibiting RORγ can potentially disrupt the pathogenic Th17 response, offering a targeted approach for managing autoimmune conditions. Moreover, its significance is underscored by numerous research publications and a growing body of evidence supporting its potential as a therapeutic target.
Taking into account RORγ's lipophilic binding site, we avoid excessively lipophilic compounds with suboptimal ADME properties. However, a minimum logD level remains essential for the favorable PK profile. Therefore, all library compounds fall within the logD range of 2 to 5.
Structure-based design was performed utilizing high-quality crystal structures, embarking on a comprehensive approach.
- 700,000 compounds were selected employing MedChem filters and clogD criteria.
- Molecular docking narrowed down the screening library to 170,000 compounds via ICM docking engine
- High-precision docking with Flare5 resulted in the top-scoring 50,000 compounds.
- A final diversity picking process resulted in a refined set of 13,000 compounds.
Detailed distributions of main physicochemical properties and representative structures are provided in the slide deck above.