3UDD

Tankyrase-1 in complex with small molecule inhibitor

3UDD の概要

• エントリーDOI: 10.2210/pdb3udd/pdb
• 分子名称: Tankyrase-1, ZINC ION, 3-(4-methoxyphenyl)-5-({[4-(4-methoxyphenyl)-5-methyl-4H-1,2,4-triazol-3-yl]sulfanyl}methyl)-1,2,4-oxadiazole, ... (6 entities in total)
• 機能のキーワード: transferase, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm: O95271
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 52713.92

構造登録者

Kirby, C.A.,Stams, T. (登録日: 2011-10-28, 公開日: 2012-02-01, 最終更新日: 2024-02-28)

主引用文献

Shultz, M.D.,Kirby, C.A.,Stams, T.,Chin, D.N.,Blank, J.,Charlat, O.,Cheng, H.,Cheung, A.,Cong, F.,Feng, Y.,Fortin, P.D.,Hood, T.,Tyagi, V.,Xu, M.,Zhang, B.,Shao, W.
[1,2,4]triazol-3-ylsulfanylmethyl)-3-phenyl-[1,2,4]oxadiazoles: antagonists of the Wnt pathway that inhibit tankyrases 1 and 2 via novel adenosine pocket binding.
J.Med.Chem., 55:1127-1136, 2012

PubMed Abstract: The Wnt signaling pathway is critical to the regulation of key cellular processes. When deregulated, it has been shown to play a crucial role in the growth and progression of multiple human cancers. The identification of small molecule modulators of Wnt signaling has proven challenging, largely due to the relative paucity of druggable nodes in this pathway. Several recent publications have identified small molecule inhibitors of the Wnt pathway, and tankyrase (TNKS) inhibition has been demonstrated to antagonize Wnt signaling via axin stabilization. Herein, we report the early hit assessment of a series of compounds previously reported to antagonize Wnt signaling. We report the biophysical, computational characterization, structure-activity relationship, and physicochemical properties of a novel series of [1,2,4]triazol-3-ylsulfanylmethyl)-3-phenyl-[1,2,4]oxadiazole inhibitors of TNKS1 and 2. Furthermore, a cocrystal structure of compound 24 complexed to TNKS1 demonstrates an alternate binding mode for PARP family member proteins that does not involve interactions with the nicotinamide binding pocket.

PubMed: 22260203
DOI: 10.1021/jm2011222

実験手法

X-RAY DIFFRACTION (1.95 Å)