ChemDiv's RORγ Library contains 13,000 compounds
RORγ (nuclear receptor) is a master regulator of Th17 cell development, therefore it is an attractive target for the treatment of autoimmune diseases.
More than 500 publications has been indexed in the Pubmed database since 2019
More than 32 newly deposited structures in the PDB database since 2019
More than 4k associated bioactivities (ChEMBL database)
RORγ’s binding site is highly lipophilic; one should avoid getting hits from too lipophilic compounds with sub-optimal ADME properties. However, some minimum level of logD is nevertheless required for activity.
1. “LogD control”: compounds are in the logD range 2 – 5.
2. Structure-based design using high quality crystal structures.
- Selection of ~700K compounds using MedChem filters and clogD criteria
- Molecular docking via ICM docking engine focused the screening library to 170K compounds
- High precision docking (Flare5) helped to select 50K compounds with top scores
- Diversity picking of selected compounds yields 13k compounds
- Distributions of basic physicochemical properties and representative structures are shown in the following slides