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

  • J Med Chem. 2022 Nov 2. doi: 10.1021/acs.jmedchem.2c01299.
Bin Hu  1 ,  Kosuke Toda  2 ,  Xiaoyu Wang  1 ,  Monika I Antczak  1 ,  Julianne Smith  2 ,  Sophie Geboers  1 ,  Gen Nishikawa  2 ,  Hongyun Li  2 ,  Dawn Dawson  2 ,  Stephen Fink  2 ,  Amar B Desai  2 ,  Noelle S Williams  1 ,  Sanford D Markowitz  2  3  4 ,  Joseph M Ready  1
Affiliations
  • 1. Department of Biochemistry, UT Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, Teas75390-9038, United States.
  • 2. Case Comprehensive Cancer Center, Cleveland, Ohio44106-5065, United States.
  • 3. Department of Medicine, Case Western Reserve University, Cleveland, Ohio44106, United States.
  • 4. Seidman Cancer Center, University Hospitals of Cleveland, Cleveland, Ohio44106, United States.
PMID: 36322935 DOI: 10.1021/acs.jmedchem.2c01299
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.

Products