7JO0
Carbonic Anhydrase IX Mimic Complexed with N-(5-sulfamoyl-1,3,4-thiadiazol-2-yl)propionamide
Summary for 7JO0
| Entry DOI | 10.2210/pdb7jo0/pdb |
| Descriptor | Carbonic anhydrase 2, ZINC ION, N-(5-sulfamoyl-1,3,4-thiadiazol-2-yl)propanamide, ... (4 entities in total) |
| Functional Keywords | carbonic anhydrase, ca inhibitor, structure guided drug design, carbonic anhydrase ii, carbonic anhydrase ix, caii, caix, sulfonamide, lyase, lyase-inhibitor complex, lyase/inhibitor |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 29502.57 |
| Authors | Andring, J.T.,McKenna, R. (deposition date: 2020-08-05, release date: 2020-11-04, Last modification date: 2023-10-18) |
| Primary citation | Andring, J.T.,Fouch, M.,Akocak, S.,Angeli, A.,Supuran, C.T.,Ilies, M.A.,McKenna, R. Structural Basis of Nanomolar Inhibition of Tumor-Associated Carbonic Anhydrase IX: X-Ray Crystallographic and Inhibition Study of Lipophilic Inhibitors with Acetazolamide Backbone. J.Med.Chem., 63:13064-13075, 2020 Cited by PubMed Abstract: This study provides a structure-activity relationship study of a series of lipophilic carbonic anhydrase (CA) inhibitors with an acetazolamide backbone. The inhibitors were tested against the tumor-expressed CA isozyme IX (CA IX), and the cytosolic CA I, CA II, and membrane-bound CA IV. The study identified several low nanomolar potent inhibitors against CA IX, with lipophilicities spanning two log units. Very potent pan-inhibitors with nanomolar potency against CA IX and sub-nanomolar potency against CA II and CA IV, and with potency against CA I one order of magnitude better than the parent acetazolamide were also identified in this study, together with compounds that displayed selectivity against membrane-bound CA IV. A comprehensive X-ray crystallographic study (12 crystal structures), involving both CA II and a soluble CA IX mimetic (CA IX-mimic), revealed the structural basis of this particular inhibition profile and laid the foundation for further developments toward more potent and selective inhibitors for the tumor-expressed CA IX. PubMed: 33085484DOI: 10.1021/acs.jmedchem.0c01390 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.607 Å) |
Structure validation
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