Carbonic Anhydrase Inhibitors Targeting Metabolism and Tumor Microenvironment
Abstract
:1. Introduction
2. Validation of CA IX/XII as Anticancer Drug Targets
2.1. Sulfonamides and Other Classes of CA inhibitors (CAIs): Selectivity for Tumor-Associated vs. Cytosolic Isoforms
2.2. Measurement of Inhibition Efficacy
2.3. Drug Design Studies Using SLC-0111 as Lead Compound
2.3.1. Modification of the SLC-0111 Benzenesulfonamide Moiety
2.3.2. Modification of the SLC-0111 Ureido Linker
2.3.3. Modification of the SLC-0111 Tail
2.3.4. Development of SLC-0111 Hybrids
3. In Vivo Studies, Preclinical and Clinical Trials of CA IX/XII Inhibitors
4. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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hCA I | hCA II | |||||
---|---|---|---|---|---|---|
Inhibitor | Single | Competition | Literature | Single | Competition | Literature |
Acetazolamide (AAZ) | 0.24 ± 0.02 | 0.29 ± 0.03 | 0.25 a [133] | 0.015 ± 0.001 | 0.022 ± 0.002 | 0.012 a [133] |
Ethoxzolamide (EZA) | 0.014 ± 0.002 | 0.016 ± 0.004 | 0.025 a [133], 0.009 b [134] | 0.010 ± 0.001 | 0.014 ± 0.002 | 0.008 a [133] |
Brinzolamide (BRZ) | 1.06 ± 0.05 | 1.12 ± 0.06 | 0.73 ± 0.04a [135] | 0.005 ± 0.001 | 0.007 ± 0.001 | 0.003 a [135] |
Furosemide (FUR) | 0.055 ± 0.005 | 0.048 ± 0.006 | 0.062 a [130] | 0.098 ± 0.009 | 0.110 ± 0.010 | 0.065 a [135] |
Dichlorophenamide (DCP) | 1.3 ± 0.1 | 1.4 ± 0.1 | 1.2 a [136] | 0.027 ± 0.002 | 0.035 ± 0.002 | 0.038 a [136] |
Indapamide (IND) | 9.2 ± 0.3 | 9.5 ± 1.0 | 51.9 a [137] | 3.22 ± 0.20 | 3.32 ± 0.31 | 2.52 a [137] |
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Angeli, A.; Carta, F.; Nocentini, A.; Winum, J.-Y.; Zalubovskis, R.; Akdemir, A.; Onnis, V.; Eldehna, W.M.; Capasso, C.; Simone, G.D.; et al. Carbonic Anhydrase Inhibitors Targeting Metabolism and Tumor Microenvironment. Metabolites 2020, 10, 412. https://doi.org/10.3390/metabo10100412
Angeli A, Carta F, Nocentini A, Winum J-Y, Zalubovskis R, Akdemir A, Onnis V, Eldehna WM, Capasso C, Simone GD, et al. Carbonic Anhydrase Inhibitors Targeting Metabolism and Tumor Microenvironment. Metabolites. 2020; 10(10):412. https://doi.org/10.3390/metabo10100412
Chicago/Turabian StyleAngeli, Andrea, Fabrizio Carta, Alessio Nocentini, Jean-Yves Winum, Raivis Zalubovskis, Atilla Akdemir, Valentina Onnis, Wagdy M. Eldehna, Clemente Capasso, Giuseppina De Simone, and et al. 2020. "Carbonic Anhydrase Inhibitors Targeting Metabolism and Tumor Microenvironment" Metabolites 10, no. 10: 412. https://doi.org/10.3390/metabo10100412