Inhibitors of 15-Prostaglandin Dehydrogenase To Potentiate Tissue Repair
| Autor: | Jacinth Naidoo, Yongyou Zhang, Jennifer M. Doran, Joseph M. Ready, Sanford D. Markowitz, Chang-Guang Wang, Sukesh Voruganti, Noelle S. Williams, Monika I. Antczak |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Prostaglandin Dehydrogenase Pharmacology 01 natural sciences Article Mice Structure-Activity Relationship 03 medical and health sciences chemistry.chemical_compound In vivo Drug Discovery Animals Humans Structure–activity relationship Enzyme Inhibitors Mice Knockout chemistry.chemical_classification 010405 organic chemistry Regeneration (biology) Small molecule In vitro 0104 chemical sciences 030104 developmental biology Enzyme chemistry Biochemistry Hydroxyprostaglandin Dehydrogenases Molecular Medicine lipids (amino acids peptides and proteins) |
| Zdroj: | Journal of Medicinal Chemistry. 60:3979-4001 |
| ISSN: | 1520-4804 0022-2623 |
| Popis: | 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, drug-like properties and in vivo activity. |
| Databáze: | OpenAIRE |
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