| Structural highlights
Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 2.011Å |
| Ligands: | , , , , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Publication Abstract from PubMed
A series of inhibitors of Autotaxin (ATX) have been developed from a high throughput screening hit, 1a, which shows an alternative binding mode to known catalytic site inhibitors. Selectivity over the hERG channel and microsomal clearance were dependent on the lipophilicity of the compounds, and this was optimised by reduction of clogD whilst maintaining high affinity ATX inhibition. Compound 15a shows good oral exposure, and concentration dependent inhibition of formation of LPA in vivo, as shown in pharmacokinetic-pharmacodynamic (PK/PD) experiments.
Development of autotaxin inhibitors: A series of tetrazole cinnamides.,Thomson CG, Le Grand D, Dowling M, Beattie D, Elphick L, Faller M, Freeman M, Hardaker E, Head V, Hemmig R, Hill J, Lister A, Pascoe D, Rieffel S, Shrestha B, Steward O, Zink F Bioorg Med Chem Lett. 2020 Nov 4:127663. doi: 10.1016/j.bmcl.2020.127663. PMID:33160025[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Thomson CG, Le Grand D, Dowling M, Beattie D, Elphick L, Faller M, Freeman M, Hardaker E, Head V, Hemmig R, Hill J, Lister A, Pascoe D, Rieffel S, Shrestha B, Steward O, Zink F. Development of autotaxin inhibitors: A series of tetrazole cinnamides. Bioorg Med Chem Lett. 2020 Nov 4:127663. doi: 10.1016/j.bmcl.2020.127663. PMID:33160025 doi:http://dx.doi.org/10.1016/j.bmcl.2020.127663
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