HA130 is a boronic acid based inhibitor of the lysoPLD activity of autotaxin (ATX). HA130 is a potent (IC50 = 28 nM), reversible inhibitor which interacts with the oxygen in active site residue T210. HA130 is selective against ATX and does not show any activity against NPP1, alkaline phosphatase, phosphodiesterase, at concentrations up to 10 microM. In addition, proteosomal chymotryptic, caspase, and typtic activities were not affected. It also showed minimal toxicity against A2058, HEK293T, and HepG2 cell lines (TD50 = 105, 83, & 2056 µM respectively). Plasma ATX activity was inhibited and circulating LPA levels decreased when administered to mice.
1) H.M.H.G. Albers et al. “Boronic acid-based inhibitor of autotaxin reveals rapid turnover of LPA in the circulation” Proc. Natl. Acad. Sci. USA, 2010, 107, 7257-7262.
2) H.M.H.G. Albers et al. “Discovery and Optimization of Boronic Acid Based Inhibitors of Autotaxin” J.Med. Chem., 2010, 53, 4958-4967.