ArticlePloS one2018
Selective inhibition of carbonic anhydrase IX over carbonic anhydrase XII in breast cancer cells using benzene sulfonamides: Disconnect between activity and growth inhibition.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 20 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 46 citations in OpenAlex.
- Motivational Interviewing and Return to Work for People with Musculoskeletal Disorders: A Systematic Mapping Review.Journal of occupational rehabilitation · 2021Pooled it
- Unraveling the Potential of Amino‑, Acylamino‑, and Ureido-Substituted 3ACS medicinal chemistry letters · 2025Article
- Development of new anticancer thiadiazole-sulfonamides as dual EGFR/carbonic anhydrase inhibitors.Future medicinal chemistry · 2025Article
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- Article
- Thiosemicarbazone-benzenesulfonamide Derivatives as Human Carbonic Anhydrases Inhibitors: Synthesis, Characterization, andAnti-cancer agents in medicinal chemistry · 2024Article
- Targeting carbonic anhydrase IX and XII isoforms with small molecule inhibitors and monoclonal antibodies.Journal of enzyme inhibition and medicinal chemistry · 2022Review
- Article
- Regulation of proton partitioning in kinase-activating acute myeloid leukemia and its therapeutic implication.Leukemia · 2022Article
- Identification of non-classical hCA XII inhibitors using combination of computational approaches for drug design and discovery.Scientific reports · 2021Article
- Inhibition of Carbonic Anhydrase Using SLC-149: Support for a Noncatalytic Function of CAIX in Breast Cancer.Journal of medicinal chemistry · 2021Article
- Carbonic anhydrase IX as a novel candidate in liquid biopsy.Journal of enzyme inhibition and medicinal chemistry · 2020Review
- Inhibitory activity against carbonic anhydrase IX and XII as a candidate selection criterion in the development of new anticancer agents.Journal of enzyme inhibition and medicinal chemistry · 2020Article
- Towards an Integral Therapeutic Protocol for Breast Cancer Based upon the New HInternational journal of molecular sciences · 2020Review
- The Anticancer Activity for the Bumetanide-Based Analogs via Targeting the Tumor-Associated Membrane-Bound Human Carbonic Anhydrase-IX Enzyme.Pharmaceuticals (Basel, Switzerland) · 2020Article
- Biophysical Characterization of Cancer-Related Carbonic Anhydrase IX.International journal of molecular sciences · 2020Article
- Review
- A New and Integral Approach to the Etiopathogenesis and Treatment of Breast Cancer Based upon Its Hydrogen Ion Dynamics.International journal of molecular sciences · 2020Review
- Carbonic anhydrase IX and acid transport in cancer.British journal of cancer · 2020Review
- Phytochemicals as Modulators of Long Non-Coding RNAs and Inhibitors of Cancer-Related Carbonic Anhydrases.International journal of molecular sciences · 2019Review
Corrections and comments
- Retraction · 2025-06-18Concerns/Issues about Image · Concerns/Issues about Results and/or Conclusions · Duplication of/in Image · Error in Image · Euphemisms for Duplication · Investigation by Journal/Publisher · Objections by Author(s) · Original Data and/or Images not Provided and/or not Available · Unreliable Results and/or Conclusions ·
- Retracted
Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
Carbonic anhydrases (CAs) have been linked to tumor progression, particularly membrane-bound CA isoform IX (CA IX). The role of CA IX in the context of breast cancer is to regulate the pH of the tumor microenvironment. In contrast to CA IX, expression of CA XII, specifically in breast cancer, is associated with better outcome despite performing the same catalytic function. In this study, we have structurally modeled the orientation of bound ureido-substituted benzene sulfonamides (USBs) within the active site of CA XII, in comparison to CA IX and cytosolic off-target CA II, to understand isoform specific inhibition. This has identified specific residues within the CA active site, which differ between isoforms that are important for inhibitor binding and isoform specificity. The ability of these sulfonamides to block CA IX activity in breast cancer cells is less effective than their ability to block activity of the recombinant protein (by one to two orders of magnitude depending on the inhibitor). The same is true for CA XII activity but now they are two to three orders of magnitude less effective. Thus, there is significantly greater specificity for CA IX activity over CA XII. While the inhibitors block cell growth, without inducing cell death, this again occurs at two orders of magnitude above the Ki values for inhibition of CA IX and CA XII activity in their respective cell types. Surprisingly, the USBs inhibited cell growth even in cells where CA IX and CA XII expression was ablated. Despite the potential for these sulfonamides as chemotherapeutic agents, these data suggest that we reconsider the role of CA activity on growth potentiation.
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