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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