title: Identification of new inhibitors for human hematopoietic prostaglandin D2 synthase among FDA-approved drugs and other compounds.
abstract: OBJECTIVE
  Hematopoietic prostaglandin D2 synthase (HPGDS) is a member of the Sigma class glutathione transferases (GSTs) catalyzing the isomerization of prostaglandin H2 to prostaglandin D2, a mediator of allergy and inflammation responses. Selective inhibitors of human HPGDS are expected to be of therapeutic importance in relieving symptoms related to allergy and asthma. Hence, a collection of diverse FDA-approved compounds was screened for potential novel applications as inhibitors of HPGDS.
  
  
  METHODS
  The catalytic activity of purified HPGDS was used for inhibition studies in vitro.
  
  
  RESULTS
  Our inhibition studies revealed 23 compounds as effective inhibitors of HPGDS with IC50 values in the low micromolar range. Erythrosine sodium, suramin, tannic acid and sanguinarine sulfate were characterized with IC50 values of 0.2, 0.3, 0.4, and 0.6 μM, respectively. Kinetic inhibition analysis showed that erythrosine sodium is a nonlinear competitive inhibitor of HPGDS, while suramin, tannic acid and sanguinarine sulfate are linear competitive inhibitors.
  
  
  CONCLUSIONS
  The results show that certain FDA-approved compounds may have pharmacological effects not previously realized that warrant further consideration in their clinical use.
authors.affiliation: Department of Neurochemistry, Stockholm University, SE-10691 Stockholm, Sweden.
authors.forename: Aslam M A
authors.initials: AM
authors.lastname: Mazari
authors.affiliation: Molecular Biology Department, Genetic Engineering and Biotechnology Division, National Research Centre, Dokki, 12311 Cairo, Egypt.
authors.forename: Usama M
authors.initials: UM
authors.lastname: Hegazy
authors.affiliation: Department of Neurochemistry, Stockholm University, SE-10691 Stockholm, Sweden. Electronic address: Bengt.Mannervik@neurochem.su.se.
authors.forename: Bengt
authors.initials: B
authors.lastname: Mannervik
mesh_terms: D017277:Drug Approval; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007700:Kinetics; D054834:Lipocalins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D004791:Enzyme Inhibitors; D054834:Lipocalins; D019746:Intramolecular Oxidoreductases; C022466:prostaglandin R2 D-isomerase
keywords: FDA-approved drugs; Glutathione transferase S1-1; HPGDS inhibitors; Prostaglandin D(2) synthase