Carbonic Anhydrase Inhibitors Targeting Cancer: Therapeutic, Immunologic, and Diagnostic Tools Targeting Isoforms IX and XII

Pastoreková, Silvia; Baráthová, Monika; Kopáček, Juraj; Pastorek, Jaromı́r

doi:10.1002/9780470508169.ch8

Cited by 6 publications

(4 citation statements)

References 151 publications

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“…Sulfonamide-based inhibitors are considered first/second generation CAIs that interact deep in the active site cleft (for example acetazolamide, dorzolamide, methazolamide et al). Currently, CAI research focuses on the design of selective inhibitors to target tumor-associated CA IX and CA XII as potential cancer treatment [ 107 ]. Though several CAIs are clinically available, few of these sulfonamide-based compounds exhibit selective inhibition.…”

Section: Improvements In Isoform Targeting Of Ca IX and Ca Xiimentioning

confidence: 99%

Cancer Drug Development of Carbonic Anhydrase Inhibitors beyond the Active Site

et al. 2018

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Carbonic anhydrases (CAs) catalyze the reversible hydration of carbon dioxide to produce bicarbonate and a proton. Multiple CA isoforms are implicated in a range of diseases, including cancer. In solid tumors, continuously dividing cells create hypoxic conditions that eventually lead to an acidic microenvironment. Hypoxic tumor cells have different mechanisms in place to regulate and adjust the surrounding microenvironment for survival. These mechanisms include expression of CA isoform IX (CA IX) and XII (CA XII). These enzymes help maintain a physiological intracellular pH while simultaneously contributing to an acidic extracellular pH, leading to tumor cell survival. Expression of CA IX and CA XII has also been shown to promote tumor cell invasion and metastasis. This review discusses the characteristics of CA IX and CA XII, their mechanism of action, and validates their prospective use as anticancer targets. We discuss the current status of small inhibitors that target these isoforms, both classical and non-classical, and their future design in order to obtain isoform-specificity for CA IX and CA XII. Biologics, such as monoclonal antibodies, monoclonal-radionuclide conjugated chimeric antibodies, and antibody-small molecule conjugates are also discussed.

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Section: Improvements In Isoform Targeting Of Ca IX and Ca Xiimentioning

confidence: 99%

Cancer Drug Development of Carbonic Anhydrase Inhibitors beyond the Active Site

et al. 2018

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“…3 Membrane-bound CA isozymes IX and XII are expressed at high levels and with a high prevalence in different tumor tissues, whose normal counterparts do not contain this protein. 4 Hypoxia often develops in solid tumors due to insufficient supply of oxygen by aberrant vasculature. 4b CA IX belongs to the mostly strongly induced proteins in response to hypoxia and was therefore suggested to serve as a marker of tumor hypoxia with possible diagnostic, prognostic and therapeutic value.…”

Section: Introductionmentioning

confidence: 99%

“…4b CA IX belongs to the mostly strongly induced proteins in response to hypoxia and was therefore suggested to serve as a marker of tumor hypoxia with possible diagnostic, prognostic and therapeutic value. 4 Maintenance of pH balance in solid tumors is challenged by their high metabolism and inadequate vasculature. The acid that is removed from cells leads to increased extracellular acidity (pH e ).…”

Section: Introductionmentioning

confidence: 99%

N-β-Glycosyl sulfamides are selective inhibitors of the cancer associated carbonic anhydrase isoforms IX and XII

Rodríguez

Maresca

Témpera

et al. 2011

Bioorganic & Medicinal Chemistry Letters

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“…Mammalian cells express different carbonic anhydrase isozymes, which differ in their tissue distribution and cellular localization [13]. Membranebound CA isozymes IX and XII are expressed at high levels and with a high prevalence in different tumor tissues, whose normal counterparts do not contain this protein [14].…”

Section: A) Anomeric Sulfonamidesmentioning

confidence: 99%