1359980-24-7Relevant articles and documents
Structure-activity relationships of small molecule autotaxin inhibitors with a discrete binding mode
Miller, Lisa M.,Keune, Willem-Jan,Castagna, Diana,Young, Louise C.,Duffy, Emma L.,Potjewyd, Frances,Salgado-Polo, Fernando,García, Paloma Engel,Semaan, Dima,Pritchard, John M.,Perrakis, Anastassis,MacDonald, Simon J. F.,Jamieson, Craig,Watson, Allan J. B.
, p. 722 - 748 (2017)
Autotaxin (ATX) is a secreted enzyme responsible for the hydrolysis of lysophosphatidylcholine (LPC) to the bioactive lysophosphatidic acid (LPA) and choline. The ATX-LPA signaling pathway is implicated in cell survival, migration, and proliferation; thus, the inhibition of ATX is a recognized therapeutic target for a number of diseases including fibrotic diseases, cancer, and inflammation, among others. Many of the developed synthetic inhibitors for ATX have resembled the lipid chemotype of the native ligand; however, a small number of inhibitors have been described that deviate from this common scaffold. Herein, we report the structure-activity relationships (SAR) of a previously reported small molecule ATX inhibitor. We show through enzyme kinetics studies that analogues of this chemotype are noncompetitive inhibitors, and by using a crystal structure with ATX we confirm the discrete binding mode.
AUTOTAXIN INHIBITORS AND USES THEREOF
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Page/Page column 102, (2012/03/11)
Described herein are compounds that are inhibitors of autotaxin. Also described are pharmaceutical compositions and medicaments that include the compounds described herein, as well as methods of using such inhibitors, alone and in combination with other compounds, for treating autotaxin-dependent or autotaxin-mediated conditions or diseases.
