Journal
JOURNAL OF MEDICINAL CHEMISTRY
Volume 65, Issue 22, Pages 15327-15343Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.jmedchem.2c01299
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Funding
- Welch Foundation
- NIH
- [I-1612]
- [R01CA216863 RM1GM142002]
- [R35CA197442]
- [R50CA211119]
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In this study, a novel class of quinoxaline amides was found to exhibit potent inhibition of 15-PGDH, resulting in elevated levels of PGE2 and promoting tissue repair and regeneration. These compounds also demonstrated good oral bioavailability and protective activity in mouse models of ulcerative colitis and recovery from bone marrow transplantation.
15-Prostaglandin dehydrogenase (15-PGDH) regulates the concentration of prostaglandin E2 in vivo. Inhibitors of 15-PGDH elevate PGE2 levels and promote tissue repair and regeneration. Here, we describe a novel class of quinoxaline amides that show potent inhibition of 15-PGDH, good oral bioavailability, and protective activity in mouse models of ulcerative colitis and recovery from bone marrow transplantation.
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