5wi0

Crystal structure of human NAMPT with fragment 2: 2-[(2-fluorophenyl)amino]-6-propylpyrimidin-4(3H)-oneCrystal structure of human NAMPT with fragment 2: 2-[(2-fluorophenyl)amino]-6-propylpyrimidin-4(3H)-one

Structural highlights 5wi0 is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: Gene: NAMPT, PBEF, PBEF1 (HUMAN) Activity: Nicotinamide phosphoribosyltransferase, with EC number 2.4.2.12 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [NAMPT_HUMAN] Catalyzes the condensation of nicotinamide with 5-phosphoribosyl-1-pyrophosphate to yield nicotinamide mononucleotide, an intermediate in the biosynthesis of NAD. It is the rate limiting component in the mammalian NAD biosynthesis pathway (By similarity). Publication Abstract from PubMed 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. Fragment-based discovery of a potent NAMPT inhibitor.,Korepanova A, Longenecker KL, Pratt SD, Panchal SC, Clark RF, Lake M, Gopalakrishnan SM, Raich D, Sun C, Petros AM Bioorg Med Chem Lett. 2017 Dec 12. pii: S0960-894X(17)31183-6. doi:, 10.1016/j.bmcl.2017.12.023. PMID:29287958 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

spinqualitylabelsall models 5wi0, resolution 2.05Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image