Carbonic anhydrase 1, 2, 9, and 12 (hCA I, II, IX, XII) (hCA I, II, IX, XII)

Human carbonic anhydrases (hCAs) are a family of zinc-containing metalloenzymes that catalyze the reversible hydration of carbon dioxide to bicarbonate and a proton [1, 5, 11]. This fundamental reaction is essential for various physiological processes, including pH homeostasis, carbon dioxide transport, and electrolyte secretion across diverse tissues [3, 5, 11]. The isoforms hCA I and II are primarily cytosolic and ubiquitous, with hCA II being one of the most efficient enzymes known; they are key therapeutic targets for treating glaucoma, edema, and epilepsy [5, 6, 16]. In contrast, hCA IX and XII are transmembrane proteins that are significantly overexpressed in many solid tumors in response to hypoxia, where they facilitate tumor cell survival and metastasis by regulating the acidic microenvironment [1, 2, 7, 10]. Drugs targeting these enzymes, such as acetazolamide and the investigational inhibitor SLC-0111, work by binding to the zinc ion in the active site to block catalytic activity [3, 7, 13, 16]. While effective, systemic inhibition of these isoforms can lead to safety concerns such as metabolic acidosis, electrolyte imbalances, and paresthesia, often necessitating the development of isoform-selective inhibitors to minimize off-target effects [14, 16].

Other names

Carbonate dehydrataseCA1CA2CA9CA12MNG250Carbonic anhydrase ICarbonic anhydrase IICarbonic anhydrase IXCarbonic anhydrase XIIhCA IhCA IIhCA IXhCA XII

Inhibition of the reversible hydration of carbon dioxide to bicarbonate and protons