Fragment Pharmacophore-Based Screening: An Efficient Approach for Discovery of New Inhibitors of Toll-Like Receptor 5

Tehran University of Medical Sciences

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Fragment Pharmacophore-Based Screening: An Efficient Approach for Discovery of New Inhibitors of Toll-Like Receptor 5 Publisher Pubmed

Hashemi H¹ ; Hassanzadeh M¹ ; Amanlou M¹

Show Affiliations

1. Faculty of Pharmacy, Department of Medicinal Chemistry and Drug Design, Development Research Center, Tehran University of Medical Sciences, P.O. Box: 14155-6451, Tehran, Iran

Source: Combinatorial Chemistry and High Throughput Screening Published:2016

Abstract

Aim and objective: 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. Material and method: Here we applied fragment pharmacophore-based virtual screening to identify novel TLR5 ligands. Results: 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. Conclusion: These compounds open a possibility to discover novel TLR5 inhibitors for the treatment of RA. © 2016 Bentham Science Publishers.

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Style	Citing Format
MLA	Hashemi H, Hassanzadeh M, Amanlou M. "Fragment Pharmacophore-Based Screening: An Efficient Approach for Discovery of New Inhibitors of Toll-Like Receptor 5." Combinatorial Chemistry and High Throughput Screening, vol. 19, no. 10, 2016, pp. 834-840.
APA	Hashemi H, Hassanzadeh M, Amanlou M (2016). Fragment Pharmacophore-Based Screening: An Efficient Approach for Discovery of New Inhibitors of Toll-Like Receptor 5. Combinatorial Chemistry and High Throughput Screening, 19(10), 834-840.
Chicago	Hashemi H, Hassanzadeh M, Amanlou M. "Fragment Pharmacophore-Based Screening: An Efficient Approach for Discovery of New Inhibitors of Toll-Like Receptor 5." Combinatorial Chemistry and High Throughput Screening 19, no. 10 (2016): 834-840.
Harvard	Hashemi H, Hassanzadeh M, Amanlou M (2016) 'Fragment Pharmacophore-Based Screening: An Efficient Approach for Discovery of New Inhibitors of Toll-Like Receptor 5', Combinatorial Chemistry and High Throughput Screening, 19(10), pp. 834-840.
Vancouver	Hashemi H, Hassanzadeh M, Amanlou M. Fragment Pharmacophore-Based Screening: An Efficient Approach for Discovery of New Inhibitors of Toll-Like Receptor 5. Combinatorial Chemistry and High Throughput Screening. 2016;19(10):834-840.
BibTex	@article{ author = {Hashemi H and Hassanzadeh M and Amanlou M}, title = {Fragment Pharmacophore-Based Screening: An Efficient Approach for Discovery of New Inhibitors of Toll-Like Receptor 5}, journal = {Combinatorial Chemistry and High Throughput Screening}, volume = {19}, number = {10}, pages = {834-840}, year = {2016} }
RIS	TY - JOUR AU - Hashemi H AU - Hassanzadeh M AU - Amanlou M TI - Fragment Pharmacophore-Based Screening: An Efficient Approach for Discovery of New Inhibitors of Toll-Like Receptor 5 JO - Combinatorial Chemistry and High Throughput Screening VL - 19 IS - 10 SP - 834 EP - 840 PY - 2016 ER -