1613512-88-1Relevant articles and documents
Development of autotaxin inhibitors: A series of zinc binding triazoles
Thomson, Christopher G.,Le Grand, Darren,Dowling, Mark,Brocklehurst, Cara E.,Chinn, Colin,Elphick, Lucy,Faller, Michael,Freeman, Mark,Furminger, Vikki,Gasser, Cornelia,Hamadi, Ahmed,Hardaker, Elizabeth,Head, Victoria,Hill, Johan C.,Janus, Diana I.,Pearce, David,Poulaud, Anne-Sophie,Stanley, Emily,Sviridenko, Lilya
supporting information, p. 2279 - 2284 (2018/05/24)
A series of inhibitors of Autotaxin (ATX) has been developed using the binding mode of known inhibitor, PF-8380, as a template. Replacement of the benzoxazolone with a triazole zinc-binding motif reduced crystallinity and improved solubility relative to PF-8380. Modification of the linker region removed hERG activity and led to compound 12 – a selective, high affinity, orally-bioavailable inhibitor of ATX. Compound 12 concentration-dependently inhibits autotaxin and formation of LPA in vivo, as shown in pharmacokinetic-pharmacodynamic experiments.
