6F1X

Complex between MTH1 and compound 7 (a 7-azaindole-2-amide derivative)

6F1X の概要

• エントリーDOI: 10.2210/pdb6f1x/pdb
• 分子名称: 7,8-dihydro-8-oxoguanine triphosphatase, 4-(3-chlorophenyl)-~{N}-ethyl-1~{H}-pyrrolo[2,3-b]pyridine-2-carboxamide, SULFATE ION, ... (4 entities in total)
• 機能のキーワード: nudix, nucleotide hydrolase, inhibitor, oncology, hydrolase
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Isoform p18: Cytoplasm. Isoform p26: Cytoplasm: P36639
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 37971.55

構造登録者

Viklund, J.,Talagas, A.,Tresaugues, L.,Andersson, M.,Ericsson, U.,Forsblom, R.,Ginman, T.,Hallberg, K.,Lindstrom, J.,Persson, L.,Silvander, C.,Rahm, F. (登録日: 2017-11-23, 公開日: 2018-03-07, 最終更新日: 2024-01-17)

主引用文献

Rahm, F.,Viklund, J.,Tresaugues, L.,Ellermann, M.,Giese, A.,Ericsson, U.,Forsblom, R.,Ginman, T.,Gunther, J.,Hallberg, K.,Lindstrom, J.,Persson, L.B.,Silvander, C.,Talagas, A.,Diaz-Saez, L.,Fedorov, O.,Huber, K.V.M.,Panagakou, I.,Siejka, P.,Gorjanacz, M.,Bauser, M.,Andersson, M.
Creation of a Novel Class of Potent and Selective MutT Homologue 1 (MTH1) Inhibitors Using Fragment-Based Screening and Structure-Based Drug Design.
J. Med. Chem., 61:2533-2551, 2018

PubMed Abstract: Recent literature has both suggested and questioned MTH1 as a novel cancer target. BAY-707 was just published as a target validation small molecule probe for assessing the effects of pharmacological inhibition of MTH1 on tumor cell survival, both in vitro and in vivo. (1) In this report, we describe the medicinal chemistry program creating BAY-707, where fragment-based methods were used to develop a series of highly potent and selective MTH1 inhibitors. Using structure-based drug design and rational medicinal chemistry approaches, the potency was increased over 10,000 times from the fragment starting point while maintaining high ligand efficiency and drug-like properties.

PubMed: 29485874
DOI: 10.1021/acs.jmedchem.7b01884

実験手法

X-RAY DIFFRACTION (1.9 Å)