Klösel I, Schmidt M, Kaindl J, Hübner H, Weikert D, Gmeiner P (2020)
Publication Type: Journal article
Publication year: 2020
Book Volume: 11
Pages Range: 1316-1323
Journal Issue: 6
DOI: 10.1021/acsmedchemlett.0c00154
Proteinase-activated receptor 2 (PAR2) is a class A G protein-coupled receptor whose activation has been associated with inflammatory diseases and cancer, thus representing a valuable therapeutic target. Pathophysiological roles of PAR2 are often characterized using peptidic PAR2 agonists. Peptidic ligands are frequently unstable in vivo and show poor bioavailability, and only a few approaches toward drug-like nonpeptidic PAR2 ligands have been described. The herein-described ligand 5a (IK187) is a nonpeptidic PAR2 agonist with submicromolar potency in a functional assay reflecting G protein activation. The ligand also showed substantial β-arrestin recruitment. The development of the compound was guided by the crystal structure of PAR2, when the C-terminal end of peptidic agonists was replaced by a small molecule based on a disubstituted phenylene scaffold. IK187 shows preferable metabolic stability and may serve as a lead compound for the development of nonpeptidic drugs addressing PAR2.
APA:
Klösel, I., Schmidt, M., Kaindl, J., Hübner, H., Weikert, D., & Gmeiner, P. (2020). Discovery of Novel Nonpeptidic PAR2 Ligands. ACS Medicinal Chemistry Letters, 11(6), 1316-1323. https://dx.doi.org/10.1021/acsmedchemlett.0c00154
MLA:
Klösel, Ilona, et al. "Discovery of Novel Nonpeptidic PAR2 Ligands." ACS Medicinal Chemistry Letters 11.6 (2020): 1316-1323.
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