Structure-activity relationship studies and biological characterization of human NAD(+)-dependent 15-hydroxyprostaglandin dehydrogenase inhibitors.

Medicinal Chemistry

Abstract

The structure-activity relationship (SAR) study of two chemotypes identified as inhibitors of the human NAD(+)-dependent 15-hydroxyprostaglandin dehydrogenase (HPGD, 15-PGDH) was conducted. Top compounds from both series displayed potent inhibition (IC50 <50 nM), demonstrate excellent selectivity towards HPGD and potently induce PGE2 production in A549 lung cancer and LNCaP prostate cancer cells.

Authors

Duveau, Damien; Yasgar, Adam; Wang, Yuhong; Hu, Xin; Kouznetsova, Jennifer; Brimacombe, Kyle; Jadhav, Ajit; Simeonov, Anton; Thomas, Craig; Maloney, David J;

Keywords

  • Cell Line, Tumor
  • Enzyme Inhibitors/ chemistry
  • Enzyme Inhibitors/ pharmacology
  • Humans
  • Hydroxyprostaglandin Dehydrogenases/ antagonists & inhibitors
  • Hydroxyprostaglandin Dehydrogenases/ metabolism
  • NAD/ antagonists & inhibitors
  • NAD/ metabolism
  • Structure-Activity Relationship

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