5WI0
Crystal structure of human NAMPT with fragment 2: 2-[(2-fluorophenyl)amino]-6-propylpyrimidin-4(3H)-one
Summary for 5WI0
| Entry DOI | 10.2210/pdb5wi0/pdb |
| Descriptor | Nicotinamide phosphoribosyltransferase, 2-[(2-fluorophenyl)amino]-6-propylpyrimidin-4(3H)-one (3 entities in total) |
| Functional Keywords | nampt, inhibitor, transferase, transferase-transferase inhibitor complex, transferase/transferase inhibitor |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 2 |
| Total formula weight | 111684.41 |
| Authors | Longenecker, K.L.,Raich, D.,Korepanova, A.V. (deposition date: 2017-07-18, release date: 2018-01-10, Last modification date: 2023-10-04) |
| Primary citation | Korepanova, A.,Longenecker, K.L.,Pratt, S.D.,Panchal, S.C.,Clark, R.F.,Lake, M.,Gopalakrishnan, S.M.,Raich, D.,Sun, C.,Petros, A.M. Fragment-based discovery of a potent NAMPT inhibitor. Bioorg. Med. Chem. Lett., 28:437-440, 2018 Cited by PubMed Abstract: NAMPT expression is elevated in many cancers, making this protein a potential target for anticancer therapy. We have carried out both NMR based and TR-FRET based fragment screens against human NAMPT and identified six novel binders with a range of potencies. Co-crystal structures were obtained for two of the fragments bound to NAMPT while for the other four fragments force-field driven docking was employed to generate a bound pose. Based on structural insights arising from comparison of the bound fragment poses to that of bound FK866 we were able to synthetically elaborate one of the fragments into a potent NAMPT inhibitor. PubMed: 29287958DOI: 10.1016/j.bmcl.2017.12.023 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.05 Å) |
Structure validation
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