1544009-05-3Relevant academic research and scientific papers
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.
ATX MODULATING AGENTS
-
, (2014/02/16)
Disclosed are bicyclic aryl compounds of formula (I), that can modulate the activity of the autotaxin (ATX) enzyme. This invention further relates to compounds that are ATX inhibitors, and methods of making and using such compounds in the treatment of demyelination due to injury or disease, as well as for treating proliferative disorders such as cancer.
