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Inhibitors of 15-Prostaglandin Dehydrogenase To Potentiate Tissue Repair

Monika I Antczak, Yongyou Zhang, Changguang Wang, Jennifer Doran, Jacinth Naidoo, Sukesh Voruganti, Noelle S Williams, Sanford D Markowitz, Joseph M Ready

J Med Chem. 2017 May 11;60(9):3979-4001.

PMID: 28398755

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.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
AP459147398 SW033291 SW033291 459147-39-8 Price
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