6UGN
Human Carbonic Anhydrase 2 complexed with SB4-205
Summary for 6UGN
| Entry DOI | 10.2210/pdb6ugn/pdb |
| Descriptor | Carbonic anhydrase 2, ZINC ION, 5,7-dimethyl-1lambda~6~,2,4-benzothiadiazine-1,1,3(2H,4H)-trione, ... (4 entities in total) |
| Functional Keywords | cyclical sulfonamide, inhibitor, lyase, lyase-lyase inhibitor complex, lyase/lyase inhibitor |
| Biological source | Homo sapiens |
| Total number of polymer chains | 1 |
| Total formula weight | 29450.55 |
| Authors | Murray, A.B.,Supuran, C.T.,McKenna, R. (deposition date: 2019-09-26, release date: 2019-12-18, Last modification date: 2023-10-11) |
| Primary citation | 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 Cited by 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: 31794211DOI: 10.1021/acs.jmedchem.9b01669 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.406 Å) |
Structure validation
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