6E8X
CA IX mimic Complexed with Steroidal Sulfamate Compound STX 140
Summary for 6E8X
| Entry DOI | 10.2210/pdb6e8x/pdb |
| Descriptor | Carbonic anhydrase 2, ZINC ION, (13alpha,17alpha)-2-methoxyestra-1,3,5,7,9,11-hexaene-3,17-diyl disulfamate, ... (4 entities in total) |
| Functional Keywords | carbonic anhydrase steroid sulfamate cancer, lyase |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 29364.39 |
| Authors | Andring, J.T.,Mckenna, R. (deposition date: 2018-07-31, release date: 2019-03-27, Last modification date: 2023-10-11) |
| Primary citation | Andring, J.T.,Dohle, W.,Tu, C.,Potter, B.V.L.,McKenna, R. 3,17 beta-Bis-sulfamoyloxy-2-methoxyestra-1,3,5(10)-triene and Nonsteroidal Sulfamate Derivatives Inhibit Carbonic Anhydrase IX: Structure-Activity Optimization for Isoform Selectivity. J. Med. Chem., 62:2202-2212, 2019 Cited by PubMed Abstract: 3,17β-Bis-sulfamoyloxy-2-methoxyestra-1,3,5(10)-triene (STX140), a bis-sulfamate derivative of the endogenous steroid 2-methoxyestradiol, has shown promising anticancer potency both in vitro and in vivo, with excellent bioavailability. Its activity against taxane-resistant xenografts makes it a potential drug candidate against triple-negative breast cancer (TNBC). These properties are linked to the ability of STX140 to act in a multitargeting fashion in vivo as a microtubule disruptor, leading to cell cycle arrest and with both proapoptotic and anti-angiogenic activities. Carbonic anhydrase IX (CA IX) is a well-established biomarker for aggressive cancers, including TNBC. This study reports, for the first time, the inhibitory activities of a series of steroidal and nonsteroidal sulfamate derivatives against CA IX in comparison to the ubiquitous CA II, with some compounds demonstrating 100-200-fold selectivity for CA IX over CA II. X-ray crystallographic studies of four of the most promising compounds reveal that isoform-specific residue interactions are responsible for the high specificity. PubMed: 30721041DOI: 10.1021/acs.jmedchem.8b01990 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.6 Å) |
Structure validation
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