Selective non-lipid modulator of LPA5 activity in human platelets.
Lysophosphatidic acid (LPA) is a potent activator of human platelets in vitro. Recently, the G protein-coupled receptor LPA5/GPR92 has been identified to be the relevant LPA receptor responsible for the activation of human platelets by LPA. In a high-throughput screening campaign we identified a diphenyl pyrazole carboxylic acid as a small-molecule inhibitor for LPA5. Confirmation for the specificity of this small molecule was achieved in human platelets as the relevant cellular in vitro model. We could confirm using antagonists for alternative LPA receptors that we identified in our work the first non-lipid, small-molecule inhibitor for LPA5/GPR92 specifically inhibiting LPA-mediated platelet activation in vitro.
Sanofi-Aventis Deutschland GmbH, Industriepark Hoechst, 65962 Frankfurt, Germany. detlef.kozian@sanofi.com
Detlef H
DH
Kozian
Andreas
A
Evers
Peter
P
Florian
Peter
P
Wonerow
Sabrina
S
Joho
Marc
M
Nazare
D001665:Binding Sites; D001792:Blood Platelets / Q000378:metabolism*; D003198:Computer Simulation; D006801:Humans; D008246:Lysophospholipids / Q000737:chemistry* / Q000494:pharmacology; D015539:Platelet Activation / Q000187:drug effects; D020033:Protein Isoforms / Q000737:chemistry / Q000378:metabolism; D017434:Protein Structure, Tertiary; D049368:Receptors, Lysophosphatidic Acid / Q000737:chemistry* / Q000378:metabolism
C512992:LPAR5 protein, human; D008246:Lysophospholipids; D020033:Protein Isoforms; D049368:Receptors, Lysophosphatidic Acid; C032881:lysophosphatidic acid