title: Structure-activity relationship studies and biological characterization of human NAD(+)-dependent 15-hydroxyprostaglandin dehydrogenase inhibitors.
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.affiliation: National Center for Advancing Translational Sciences, National Institutes of Health, 9800 Medical Center Drive, Rockville, MD 20850, United States.
authors.forename: Damien Y
authors.initials: DY
authors.lastname: Duveau
authors.affiliation: National Center for Advancing Translational Sciences, National Institutes of Health, 9800 Medical Center Drive, Rockville, MD 20850, United States.
authors.forename: Adam
authors.initials: A
authors.lastname: Yasgar
authors.affiliation: National Center for Advancing Translational Sciences, National Institutes of Health, 9800 Medical Center Drive, Rockville, MD 20850, United States.
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: National Center for Advancing Translational Sciences, National Institutes of Health, 9800 Medical Center Drive, Rockville, MD 20850, United States.
authors.forename: Xin
authors.initials: X
authors.lastname: Hu
authors.affiliation: National Center for Advancing Translational Sciences, National Institutes of Health, 9800 Medical Center Drive, Rockville, MD 20850, United States.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Kouznetsova
authors.affiliation: National Center for Advancing Translational Sciences, National Institutes of Health, 9800 Medical Center Drive, Rockville, MD 20850, United States.
authors.forename: Kyle R
authors.initials: KR
authors.lastname: Brimacombe
authors.affiliation: National Center for Advancing Translational Sciences, National Institutes of Health, 9800 Medical Center Drive, Rockville, MD 20850, United States.
authors.forename: Ajit
authors.initials: A
authors.lastname: Jadhav
authors.affiliation: National Center for Advancing Translational Sciences, National Institutes of Health, 9800 Medical Center Drive, Rockville, MD 20850, United States.
authors.forename: Anton
authors.initials: A
authors.lastname: Simeonov
authors.affiliation: National Center for Advancing Translational Sciences, National Institutes of Health, 9800 Medical Center Drive, Rockville, MD 20850, United States.
authors.forename: Craig J
authors.initials: CJ
authors.lastname: Thomas
authors.affiliation: National Center for Advancing Translational Sciences, National Institutes of Health, 9800 Medical Center Drive, Rockville, MD 20850, United States. Electronic address: maloneyd@mail.nih.gov.
authors.forename: David J
authors.initials: DJ
authors.lastname: Maloney
mesh_terms: D045744:Cell Line, Tumor; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D006911:Hydroxyprostaglandin Dehydrogenases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009243:NAD / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D009243:NAD; D006911:Hydroxyprostaglandin Dehydrogenases; C035859:15-hydroxyprostaglandin dehydrogenase
keywords: 15-PGDH; HPGD; Inhibitor; PGE(2); Prostaglandin