6UGP

Human Carbonic Anhydrase 2 complexed with SB4-206

6UGP の概要

• エントリーDOI: 10.2210/pdb6ugp/pdb
• 分子名称: Carbonic anhydrase 2, ZINC ION, 5-chloro-1lambda~6~,2,4-benzothiadiazine-1,1,3(2H,4H)-trione, ... (5 entities in total)
• 機能のキーワード: cyclical sulfonamide, inhibitor, lyase, lyase-lyase inhibitor complex, lyase/lyase inhibitor
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 29585.48

構造登録者

Murray, A.B.,Lomelino, C.L.,McKenna, R. (登録日: 2019-09-26, 公開日: 2019-12-18, 最終更新日: 2023-10-11)

主引用文献

Bua, S.,Lomelino, C.,Murray, A.B.,Osman, S.M.,ALOthman, Z.A.,Bozdag, M.,Abdel-Aziz, H.A.,Eldehna, W.M.,McKenna, R.,Nocentini, A.,Supuran, C.T.
"A Sweet Combination": Developing Saccharin and Acesulfame K Structures for Selectively Targeting the Tumor-Associated Carbonic Anhydrases IX and XII.
J.Med.Chem., 63:321-333, 2020

PubMed Abstract: The sweeteners saccharin () and acesulfame K () recently entered the topic of anticancer human carbonic anhydrase (CA, EC 4.2.1.1) inhibitors, as they showed to selectively inhibit the tumor-associated CAs IX/XII over ubiquitous CAs. A drug design strategy is here reported, which took and as leads and produced a series of 2-benzo[][1,2,4]thiadiazin-3(4)-one-1,1-dioxides (). Many derivatives showed greater potency (s-CA IX 19.1-408.5 nM) and selectivity (II/IX SI 2-76) than the leads (s-CA IX 103, 2400 nM; II/IX-SI 56, >4) against CA IX/XII over off-target isoforms. A thorough X-ray crystallographic study depicted their binding mode to both CA II and IX-mimic. The most representative were characterized in vitro for their antitumor activity against A549, PC-3, and HCT-116 cancer cell lines both in normoxia and hypoxia. The two most effective compounds were assayed for their effect on several apoptosis markers, identifying promising leads for the development of new anticancer drugs.

PubMed: 31794211
DOI: 10.1021/acs.jmedchem.9b01669

実験手法

X-RAY DIFFRACTION (1.306 Å)