Orally Bioavailable Quinoxaline Inhibitors of 15-Prostaglandin Dehydrogenase (15-PGDH) Promote Tissue Repair and Regeneration

口服生物可利用的喹喔啉 15-前列腺素脱氢酶 (15-PGDH) 抑制剂促进组织修复和再生

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作者:Bin Hu, Kosuke Toda, Xiaoyu Wang, Monika I Antczak, Julianne Smith, Sophie Geboers, Gen Nishikawa, Hongyun Li, Dawn Dawson, Stephen Fink, Amar B Desai, Noelle S Williams, Sanford D Markowitz, Joseph M Ready

Abstract

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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