Skip to Main content Skip to Navigation
Journal articles

Discovery of nanomolar ligands with novel scaffolds for the histamine H4 receptor by virtual screening

Abstract : The involvement of histamine H4 receptor (H4R) in immune cells chemotaxis and mediator release makes it an attractive target for the treatment of inflammation disorders. A decade of medicinal chemistry efforts has led to several promising ligands, although the chemical structures described so far possesses a singular limited diversity. We report here the discovery of novel structures, belonging to completely different scaffolds. The virtual screening was planed as a two-steps process. First, using a “scout screening” methodology, we have experimentally probed the H4R ligand binding site using a small size chemical library with very diverse structures, and identified a hit that further assist us in refining a raw 3D homology model. Second, the refined 3D model was used to conduct a widened virtual screening. This two-steps strategy proved to be very successful, both in terms of structural diversity and hit rate (23%). Moreover, the hits have high affinity for the H4R, with most potent ligands in the nanomolar range.
Document type :
Journal articles
Complete list of metadatas

https://hal-normandie-univ.archives-ouvertes.fr/hal-02046295
Contributor : Madeleine Roux-Merlin <>
Submitted on : Friday, February 22, 2019 - 3:40:08 PM
Last modification on : Saturday, October 3, 2020 - 3:12:19 AM

Identifiers

Citation

N. Levoin, O. Labeeuw, X. Billot, T. Calmels, Denis Danvy, et al.. Discovery of nanomolar ligands with novel scaffolds for the histamine H4 receptor by virtual screening. European Journal of Medicinal Chemistry, Elsevier, 2017, 125, pp.565-572. ⟨10.1016/j.ejmech.2016.09.074⟩. ⟨hal-02046295⟩

Share

Metrics

Record views

98