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

Bioorg Med Chem Lett. 2014 Jan 15;24(2):630-5. doi: 10.1016/j.bmcl.2013.11.081. Epub 2013 Dec 4.

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.

Keywords: 15-PGDH; HPGD; Inhibitor; PGE(2); Prostaglandin.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • 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

Substances

  • Enzyme Inhibitors
  • NAD
  • Hydroxyprostaglandin Dehydrogenases
  • 15-hydroxyprostaglandin dehydrogenase