4M7B

Human tankyrase 2 - catalytic Parp domain in complex with an inhibitor UPF1854

Summary for 4M7B

• Entry DOI: 10.2210/pdb4m7b/pdb
• Related: 3P0Q
• Descriptor: Tankyrase-2, ZINC ION, 4-{2-[(6-methyl[1,2,4]triazolo[4,3-b]pyridazin-8-yl)amino]ethyl}phenol, ... (5 entities in total)
• Functional Keywords: diphtheria toxin like adp-ribose transferase domain, poly adp-ribosylation, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: Q9H2K2
• Total number of polymer chains: 2
• Total formula weight: 55653.20

Authors

Karlberg, T.,Camaioni, E.,Schuler, H. (deposition date: 2013-08-12, release date: 2014-03-12, Last modification date: 2023-09-20)

Primary citation

Liscio, P.,Carotti, A.,Asciutti, S.,Karlberg, T.,Bellocchi, D.,Llacuna, L.,Macchiarulo, A.,Aaronson, S.A.,Schuler, H.,Pellicciari, R.,Camaioni, E.
Design, Synthesis, Crystallographic Studies, and Preliminary Biological Appraisal of New Substituted Triazolo[4,3-b]pyridazin-8-amine Derivatives as Tankyrase Inhibitors.
J.Med.Chem., 57:2807-2812, 2014

PubMed Abstract: Searching for selective tankyrases (TNKSs) inhibitors, a new small series of 6,8-disubstituted triazolo[4,3-b]piridazines has been synthesized and characterized biologically. Structure-based optimization of the starting hit compound NNL (3) prompted us to the discovery of 4-(2-(6-methyl-[1,2,4]triazolo[4,3-b]pyridazin-8-ylamino)ethyl)phenol (12), a low nanomolar selective TNKSs inhibitor working as NAD isostere as ascertained by crystallographic analysis. Preliminary biological data candidate this new class of derivatives as a powerful pharmacological tools in the unraveling of TNKS implications in physiopathological conditions.

PubMed: 24527792
DOI: 10.1021/jm401356t

Experimental method

X-RAY DIFFRACTION (1.95 Å)