4KRS

Tankyrase-1 complexed with small molecule inhibitor

Summary for 4KRS

• Entry DOI: 10.2210/pdb4krs/pdb
• Descriptor: Tankyrase-1, ZINC ION, SULFATE ION, ... (5 entities in total)
• Functional Keywords: transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: O95271
• Total number of polymer chains: 2
• Total formula weight: 51921.24

Authors

Stams, T.,Kirby, C. (deposition date: 2013-05-17, release date: 2013-08-28, Last modification date: 2024-02-28)

Primary citation

Shultz, M.D.,Majumdar, D.,Chin, D.N.,Fortin, P.D.,Feng, Y.,Gould, T.,Kirby, C.A.,Stams, T.,Waters, N.J.,Shao, W.
Structure-Efficiency Relationship of [1,2,4]Triazol-3-ylamines as Novel Nicotinamide Isosteres that Inhibit Tankyrases.
J.Med.Chem., 56:7049-7059, 2013

PubMed Abstract: Tankyrases 1 and 2 are members of the poly(ADP-ribose) polymerase (PARP) family of enzymes that modulate Wnt pathway signaling. While amide- and lactam-based nicotinamide mimetics that inhibit tankyrase activity, such as XAV939, are well-known, herein we report the discovery and evaluation of a novel nicotinamide isostere that demonstrates selectivity over other PARP family members. We demonstrate the utilization of lipophilic efficiency-based structure-efficiency relationships (SER) to rapidly drive the evaluation of this series. These efforts led to a series of selective, cell-active compounds with solubility, physicochemical, and in vitro properties suitable for further optimization.

PubMed: 23879431
DOI: 10.1021/jm400826j

Experimental method

X-RAY DIFFRACTION (2.29 Å)