Discovery of an Oral Potent Selective Inhibitor of Hematopoietic Prostaglandin D Synthase (HPGDS)

  • ACS Med Chem Lett. 2010 Feb 2;1(2):59-63. doi: 10.1021/ml900025z.
Chris P Carron  1 ,  John I Trujillo  1 ,  Kirk L Olson  1 ,  Wei Huang  1 ,  Bruce C Hamper  1 ,  Tom Dice  1 ,  Bradley E Neal  1 ,  Matthew J Pelc  1 ,  Jacqueline E Day  1 ,  Douglas C Rohrer  1 ,  James R Kiefer  1 ,  Joseph B Moon  1 ,  Barbara A Schweitzer  1 ,  Tanisha D Blake  1 ,  Steve R Turner  1 ,  Rhonda Woerndle  1 ,  Brenda L Case  1 ,  Christine P Bono  1 ,  Vickie M Dilworth  1 ,  Christie L Funckes-Shippy  1 ,  Becky L Hood  1 ,  Gina M Jerome  1 ,  Christine M Kornmeier  1 ,  Melissa R Radabaugh  1 ,  Melanie L Williams  1 ,  Michael S Davies  1 ,  Craig D Wegner  1 ,  Dean J Welsch  1 ,  William M Abraham  2 ,  Chad J Warren  1 ,  Martin E Dowty  1 ,  Fengmei Hua  1 ,  Anup Zutshi  1 ,  Jerry Z Yang  1 ,  Atli Thorarensen  1
Affiliations
  • 1. Pfizer Global Research and Development, 700 Chesterfield Parkway West, Chesterfield, Missouri 63017.
  • 2. Department of Research, Mount Sinai Medical Center, 4300 Alton Road, Miami Beach, Florida 33140.
Abstract

Hematopoietic Prostaglandin D Synthase (HPGDS) is primarly expressed in mast cells, antigen-presenting cells, and Th-2 cells. HPGDS converts PGH2 into PGD2, a mediator thought to play a pivotal role in airway Allergy and inflammatory processes. In this letter, we report the discovery of an orally potent and selective inhibitor of HPGDS that reduces the antigen-induced response in allergic sheep.

Keywords
Hematopoietic prostaglandin D synthase (HPGDS); PGD2; PGH2; airway allergy; inflammatory processes, cyclooxygenase (COX).
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