5NSP
Crystal structure of TNKS2 in complex with OD334
Summary for 5NSP
| Entry DOI | 10.2210/pdb5nsp/pdb |
| Descriptor | Tankyrase-2, ZINC ION, SULFATE ION, ... (8 entities in total) |
| Functional Keywords | tnks2, artd6, inhibitor, parp5b, adp-ribosyltransferase, transferase |
| Biological source | Homo sapiens (Human) More |
| Total number of polymer chains | 4 |
| Total formula weight | 55855.62 |
| Authors | Nkizinkiko, Y.,Haikarainen, T.,Lehtio, L. (deposition date: 2017-04-26, release date: 2017-11-29, Last modification date: 2024-01-17) |
| Primary citation | Anumala, U.R.,Waaler, J.,Nkizinkiko, Y.,Ignatev, A.,Lazarow, K.,Lindemann, P.,Olsen, P.A.,Murthy, S.,Obaji, E.,Majouga, A.G.,Leonov, S.,von Kries, J.P.,Lehtio, L.,Krauss, S.,Nazare, M. Discovery of a Novel Series of Tankyrase Inhibitors by a Hybridization Approach. J. Med. Chem., 60:10013-10025, 2017 Cited by PubMed Abstract: A structure-guided hybridization approach using two privileged substructures gave instant access to a new series of tankyrase inhibitors. The identified inhibitor 16 displays high target affinity on tankyrase 1 and 2 with biochemical and cellular IC values of 29 nM, 6.3 nM and 19 nM, respectively, and high selectivity toward other poly (ADP-ribose) polymerase enzymes. The identified inhibitor shows a favorable in vitro ADME profile as well as good oral bioavailability in mice, rats, and dogs. Critical for the approach was the utilization of an appropriate linker between 1,2,4-triazole and benzimidazolone moieties, whereby a cyclobutyl linker displayed superior affinity compared to a cyclohexane and phenyl linker. PubMed: 29155568DOI: 10.1021/acs.jmedchem.7b00883 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.3 Å) |
Structure validation
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