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ID: ALA4049436
Journal: J Med Chem
Title: Inhibitors of 15-Prostaglandin Dehydrogenase To Potentiate Tissue Repair.
Authors: Antczak MI, Zhang Y, Wang C, Doran J, Naidoo J, Voruganti S, Williams NS, Markowitz SD, Ready JM.
Abstract: The enzyme 15-prostaglandin dehydrogenase (15-PGDH) catalyzes the first step in the degradation of prostaglandins including PGE2. It is a negative regulator of tissue repair and regeneration in multiple organs. Accordingly, inhibitors of 15-PGDH are anticipated to elevate in vivo levels of PGE2 and to promote healing and tissue regeneration. The small molecule SW033291 (1) inhibits 15-PGDH with Ki = 0.1 nM in vitro, doubles PGE2 levels in vivo, and shows efficacy in mouse models of recovery from bone marrow transplantation, ulcerative colitis, and partial hepatectomy. Here we describe optimized variants of 1 with improved solubility, druglike properties, and in vivo activity.
CiteXplore: 28398755