Fragment pharmacophore-based screening: an efficient approach for discovery of new inhibitors of Toll-Like Receptor 5.

Fragment pharmacophore-based screening: an efficient approach for discovery of new inhibitors of Toll-Like Receptor 5.
Comb Chem High Throughput Screen. 2016 Sep 7;
Authors: Hashemi H, Hasanzadeh M, Amanlou M
Abstract
Rheumatoid Arthritis (RA) is a progressing autoimmune inflammatory disease of joint, hallmarked by inflammation, pain and atrophy of bones. Toll-like receptor 5 (TLR5) is a novel inflammatory mediator in RA, and TLR5 inhibitors are speculated to have a therapeutic potential for the treatment of RA. Here we applied fragment pharmacophore-based virtual screening to identify novel TLR5 ligands. Among compounds collected from Otava peptidomimetic compounds, Maybridge fragment and ZINC libraries, 3355 compounds were selected for docking into the flagellin-binding site of TLR5. 16 compounds with the required interaction, critical amino acid residues and the binding free energies <-7 kcal/mol were identified as potential TLR5 inhibitors, one of which was followed up by molecular dynamics simulation. These compounds open a possibility to discover novel TLR5 inhibitors for the treatment of RA.
PMID: 27604956 [PubMed - as supplied by publisher]

Source: Combinatorial Chemistry and High Throughput Screening - September 6, 2016 Category: Chemistry Authors: Hashemi H, Hasanzadeh M, Amanlou M Tags: Comb Chem High Throughput Screen Source Type: research