Identification of new inhibitors for human hematopoietic prostaglandin D-2 synthase among FDA-approved drugs and other compounds
2015 (English)In: Chemico-Biological Interactions, ISSN 0009-2797, E-ISSN 1872-7786, Vol. 229, 91-99 p.Article in journal (Refereed) Published
Objective: Hematopoietic prostaglandin D-2 synthase (HPGDS) is a member of the Sigma class glutathione transferases (GSTs) catalyzing the isomerization of prostaglandin H-2 to prostaglandin D-2, 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 mu M, 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. Conclusion: The results show that certain FDA-approved compounds may have pharmacological effects not previously realized that warrant further consideration in their clinical use.
Place, publisher, year, edition, pages
2015. Vol. 229, 91-99 p.
Prostaglandin D-2 synthase, FDA-approved drugs, HPGDS inhibitors, Glutathione transferase S1-1
Biochemistry and Molecular Biology Pharmacology and Toxicology
Research subject Neurochemistry with Molecular Neurobiology
IdentifiersURN: urn:nbn:se:su:diva-117004DOI: 10.1016/j.cbi.2015.01.014ISI: 000352050800011PubMedID: 25603235OAI: oai:DiVA.org:su-117004DiVA: diva2:810775
FunderSwedish Cancer SocietySwedish Research Council