4n4v | pdb_00004n4v

Co-crystal structure of tankyrase 1 with compound 4 [(4S)-3-{trans-4-[6-amino-5-(pyrimidin-2-yl)pyridin-3-yl]cyclohexyl}-5,5-dimethyl-4-phenyl-1,3-oxazolidin-2-one]

spinqualitylabelsall models 4n4v, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4n4v 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: 2GY, ZN Related: 4k4f, 4n3r, 4n4t Gene: TNKS, PARP5A, PARPL, TIN1, TINF1, TNKS1 (HUMAN) Activity: NAD(+) ADP-ribosyltransferase, with EC number 2.4.2.30 Resources: FirstGlance, OCA, RCSB, PDBsum Publication Abstract from PubMed Aberrant activation of the Wnt pathway has been implicated in the development and formation of many cancers. TNKS inhibition has been shown to antagonize Wnt signaling via Axin stabilization in APC mutant colon cancer cell lines. We employed structure-based design to identify a series of 2-aminopyridine oxazolidinones as potent and selective TNKS inhibitors. These compounds exhibited good enzyme and cell potency as well as selectivity over other PARP isoforms. Co-crystal structures of these 2-aminopyridine oxazolidinones complexed to TNKS reveal an induced-pocket binding mode that does not involve interactions with the nicotinamide binding pocket. Oral dosing of lead compounds 3 and 4 resulted in significant effects on several Wnt-pathway biomarkers in a three day DLD-1 mouse tumor PD model. Structure-based design of 2-aminopyridine oxazolidinones as potent and selective tankyrase inhibitors.,Huang H, Guzman-Perez A, Acquaviva L, Berry V, Bregman H, Dovey J, Gunaydin H, Huang X, Huang L, Saffran D, Serafino R, Schneider S, Wilson C, DiMauro EF ACS Med Chem Lett. 2013 Oct 21;4(12):1218-23. doi: 10.1021/ml4003315. eCollection, 2013 Dec 12. PMID:24900633 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Poly (ADP-ribose) polymerase

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