Autotaxin inhibitors

Virtual screening approaches for the identification of non-lipid autotaxin inhibitors. Bioorganic et Medicinal Chemistry, 16, 1784—1795. 

Zhang H, Xu X, Gajewiak J, Tsukahara R, Fujiwara Y, Liu J, Fells J I, Perygin D, Parrill A L, Tigyi G and Prestwich G D (2009), Dual activity lysophosphatidic acid receptor pan-antagonist/autotaxin inhibitor reduces breast cancer cell migration in vitro and causes tumor regression in vivo . Cancer Res, 69, 5441-9. 

Amira Pharmaceuticals Inc (2012) Autotaxin inhibitors and uses thereof. Patent WO2012/24620... 

Cui P, Tomsig JL, McCalmont WF, Lee S, Becker CJ, Lynch KR, Macdonald TL. Synthesis and biological evaluation of phosphonate derivatives as autotaxin (ATX) inhibitors. Bioorg. Med. 

In this paper, Prestwich et al. also described the synthesis of two phos-phonothioates 4a and 4b (Figure 4) for their evaluation as inhibitors of autotaxin. 

Cyclic phosphatidic acid analogs (see Section 2.1, Inhibitors of autotaxin) have also been studied for potential activities on respiratory and cardiovascular functions (06EJP27). Oleyl cPa 8 showed that in anesthetized rats. 

Inhibitors of autotaxin/lysophospholipase D have yet to be identified. However, inhibitors of sphingosine kinase, such as dimethylsphingosine and dihydrosphingosine, potentiate the cell death induced by recognized anticancer treatments, are effective in drug- and radiation-resistant cancer cells and have shown significant inhibition of cancers in preclinical trials (Cuvillier and Levade, 2003). 

---