9RRP

Tankyrase 2 in complex with an inhibitor

This is a non-PDB format compatible entry.

Summary for 9RRP

• Entry DOI: 10.2210/pdb9rrp/pdb
• Descriptor: Poly [ADP-ribose] polymerase tankyrase-2, GLYCEROL, DI(HYDROXYETHYL)ETHER, ... (7 entities in total)
• Functional Keywords: inhibitor, transferase, tankyrase 2, artd6, parp5b
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 25643.19

Authors

Bosetti, C.,Lehtio, L. (deposition date: 2025-06-27, release date: 2026-01-28)

Primary citation

Ouzounthanasis, K.A.,Bosetti, C.,Alaviuhkola, J.,Dhakar, S.S.,Mantzourani, C.,Kokotou, M.G.,Kanetidis, D.,Lehtio, L.,Koumbis, A.E.
Discovery of Fused Isoquinolinone/Triazole as a Scaffold for Tankyrase and PARP Inhibition.
J.Med.Chem., 69:330-351, 2026

PubMed Abstract: A series of fused isoquinolinone/triazole hybrids were designed and prepared applying a unified versatile synthetic strategy. This practically involved three steps, a novel one-pot CuAAc "click" reaction-iodination process, an amidation and a copper-catalyzed intramolecular Ullmann cyclization and was found to be applicable for a variety of substitutions patterns on the main framework. Some of those synthesized hybrids were tested for selected ADP-ribosyltransferases and found to display nanomolar potency against TNKS2, whereas selectivity was also observed in comparison to other tested PARPs. The SAR studies divulged key structural features which are responsible for this selectivity. Moreover, the identification of the binding site of those selective derivatives using X-ray crystallography revealed that they are accommodated in the nicotinamide binding subsite while certain groups extend toward a hydrophobic pocket unique to tankyrases.

PubMed: 41455111
DOI: 10.1021/acs.jmedchem.5c02481

Experimental method

X-RAY DIFFRACTION (2.05 Å)