Three novel series were generated in order to mimic the pharmacophoric features displayed by lead compound AM095, a Lysophosphatidic acid (LPA1) receptor antagonist. Biological evaluation of this array of putative LPA1 antagonists led us to the discovery of three novel series of inhibitors of the ecto-enzyme Autotaxin (ATX), responsible for LPA production in blood, with potencies in the range 1 – 4 μM accompanied with good (> 100 μg/mL) solubility.
- drug discovery
- lysophosphatidic acid
- lead compound
Castagna, D., Duffy, E. L., Semaan, D., Young, L. C., Pritchard, J. M., Macdonald, S. J. F., ... Watson, A. J. B. (2015). Identification of a novel class of autotaxin inhibitors through cross-screening. MedChemComm, 2015(6), 1149-1155. https://doi.org/10.1039/C5MD00081E