7r54 › Citations

Structure-Based Optimization of a Fragment-like TLR8 Binding Screening Hit to an In Vivo Efficacious TLR7/8 Antagonist.

Betschart C, Faller M, Zink F, Hemmig R, Blank J, Vangrevelinghe E, Bourrel M, Glatthar R, Behnke D, Barker K, Heizmann A, Angst D, Nimsgern P, Jacquier S, Junt T, Zipfel G, Ruzzante G, Loetscher P, Limonta S, Hawtin S, Andre CB, Boulay T, Feifel R, Knoepfel T
ACS Med Chem Lett 13 658-664 (2022)
Related entries: 7r52, 7r53

Cited: 2 times
EuropePMC logo PMID: 35450354

Abstract

Inappropriate activation of TLR7 and TLR8 is linked to several autoimmune diseases, such as lupus erythematosus. Here we report on the efficient structure-based optimization of the inhibition of TLR8, starting from a co-crystal structure of a small screening hit. Further optimization of the physicochemical properties for cellular potency and expansion of the structure-activity relationship for dual potency finally resulted in a highly potent TLR7/8 antagonist with demonstrated in vivo efficacy after oral dosing.

Reviews - 7r54 mentioned but not cited (1)

  1. Host-pathogen protein-nucleic acid interactions: A comprehensive review. Jain A, Mittal S, Tripathi LP, Nussinov R, Ahmad S. Comput Struct Biotechnol J 20 4415-4436 (2022)


Reviews citing this publication (1)

  1. Recent Advances on Small-Molecule Antagonists Targeting TLR7. Zheng H, Wu P, Bonnet PA. Molecules 28 634 (2023)


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