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Discovery of Irbesartan Derivatives as BLT2 Agonists by Virtual Screening.

ABSTRACT: Leuktriene B4 receptor 2 (BLT2) is a G-protein coupled receptor modulation of which is discussed to be a therapeutic option for healing of intestinal lesions. In this work, new BLT2 agonists were identified by a virtual screening of a repurposing library and in vitro assay of the most promising compounds. Irbesartan, an approved type-1 angiotensin II receptor (AT1) antagonist, was identified as a moderate BLT2 agonist. An initial SAR study on the irbesartan scaffold was performed resulting in the discovery of a new potent BLT2 agonist (8f, EC₅₀ = 67.6 nM). Irbesartan and 8f were shown to promote proliferation of epithelial colon cells, an effect which was reversible by a BLT2 antagonist.

SUBMITTER: Hernandez-Olmos V

PROVIDER: S-EPMC8366018 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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Discovery of Irbesartan Derivatives as BLT2 Agonists by Virtual Screening.

Hernandez-Olmos Victor V Heering Jan J Bischoff-Kont Iris I Kaps Alexander A Rajkumar Rinusha R Liu Ting T Fürst Robert R Steinhilber Dieter D Proschak Ewgenij E

ACS medicinal chemistry letters 20210706 8

Leuktriene B4 receptor 2 (BLT2) is a G-protein coupled receptor modulation of which is discussed to be a therapeutic option for healing of intestinal lesions. In this work, new BLT2 agonists were identified by a virtual screening of a repurposing library and <i>in vitro</i> assay of the most promising compounds. Irbesartan, an approved type-1 angiotensin II receptor (AT1) antagonist, was identified as a moderate BLT2 agonist. An initial SAR study on the irbesartan scaffold was performed resultin ...[more]

PMID: 34413955

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