1544664-03-0Relevant articles and documents
Discovery of Potent Selective Nonzinc Binding Autotaxin Inhibitor BIO-32546
Ma, Bin,Zhang, Lei,Sun, Lihong,Xin, Zhili,Kumaravel, Gnanasambandam,Marcotte, Douglas,Chodaparambil, Jayanth V.,Wang, Qin,Wehr, Angela,Jing, Jing,Hong, Victor Sukbong,Wang, Ti,Huang, Carol,Shao, Zhaohui,Mi, Sha
, p. 1124 - 1129 (2021/06/30)
Autotaxin (ATX) is a lysophospholipase D that is the main enzyme responsible for generating LPA in body fluids. Although ATX was isolated from a conditioned medium of melanoma cells, later it was discovered to play a critical role in vascular and neuronal development. ATX has also been implicated in primary brain tumor, fibrosis, and rheumatoid arthritis, as well as neurological diseases such as multiple sclerosis, Alzheimer's disease, and neuropathic pain. As ATX and LPA levels are increased upon neuronal injury, a selective ATX inhibitor could provide a new approach to treat neuropathic pain. Herein we describe the discovery of a novel series of nonzinc binding reversible ATX inhibitors, particularly a potent, selective, orally bioavailable, brain-penetrable tool compound BIO-32546, as well as its synthesis, X-ray cocrystal structure, pharmacokinetics, and in vivo efficacy.
COMPOUNDS THAT ARE S1P MODULATING AGENTS AND/OR ATX MODULATING AGENTS
-
Page/Page column 186; 187; 188, (2014/02/16)
Compounds of formula (I) can modulate the activity of one or more S1P receptors and/or the activity of autotaxin (ATX).
