6Y5M
Crystal structure of mouse Autotaxin in complex with compound 1a
Summary for 6Y5M
| Entry DOI | 10.2210/pdb6y5m/pdb |
| Descriptor | Ectonucleotide pyrophosphatase/phosphodiesterase family member 2, alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-alpha-D-mannopyranose-(1-6)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (9 entities in total) |
| Functional Keywords | zinc binding hydrolase activity inhibitor, hydrolase |
| Biological source | Mus musculus (house mouse) |
| Total number of polymer chains | 1 |
| Total formula weight | 97920.19 |
| Authors | Faller, M.,Zink, F. (deposition date: 2020-02-25, release date: 2020-11-18, Last modification date: 2024-10-23) |
| Primary citation | Thomson, C.G.,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., 31:127663-127663, 2021 Cited by PubMed Abstract: 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. PubMed: 33160025DOI: 10.1016/j.bmcl.2020.127663 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.011 Å) |
Structure validation
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