1034297-69-2Relevant articles and documents
Identification of indole inhibitors of human hematopoietic prostaglandin D2 synthase (hH-PGDS)
Edfeldt, Fredrik,Even?s, Johan,Lepist?, Matti,Ward, Alison,Petersen, Jens,Wissler, Lisa,Rohman, Mattias,Sivars, Ulf,Svensson, Karin,Perry, Matthew,Feierberg, Isabella,Zhou, Xiao-Hong,Hansson, Thomas,Narjes, Frank
, p. 2496 - 2500 (2015)
Abstract Human H-PGDS has shown promise as a potential target for anti-allergic and anti-inflammatory drugs. Here we describe the discovery of a novel class of indole inhibitors, identified through focused screening of 42,000 compounds and evaluated using a series of hit validation assays that included fluorescence polarization binding, 1D NMR, ITC and chromogenic enzymatic assays. Compounds with low nanomolar potency, favorable physico-chemical properties and inhibitory activity in human mast cells have been identified. In addition, our studies suggest that the active site of hH-PGDS can accommodate larger structural diversity than previously thought, such as the introduction of polar groups in the inner part of the binding pocket.
