Carbonic anhydrase II and Carbonic anhydrase IX (CA II and CA IX)

Carbonic anhydrase II (CA II) and Carbonic anhydrase IX (CA IX) are zinc-containing metalloenzymes of the α-carbonic anhydrase family that catalyze the reversible hydration of carbon dioxide to bicarbonate and protons, a reaction crucial for pH regulation and homeostasis in many tissues. CA II is one of the most active isoforms and is found widely in erythrocytes, kidneys, and the eyes, where it plays essential roles in physiological bicarbonate transport and pH regulation. Pathologically, its inhibition underlies therapies for glaucoma and some types of epilepsy[3][5]. CA IX is a transmembrane enzyme highly overexpressed in many hypoxic tumors, where it mediates extracellular acidification that assists tumor survival, proliferation, and metastasis, and serves both as a prognostic biomarker and an emerging anticancer drug target. Specific inhibitors of CA IX are under development for anticancer therapy, as it is largely restricted to tumors and minimally expressed in most normal tissues[1][2].

Other names

CA2 (for Carbonic anhydrase II)CAIX, CA-IX, or G250/MPN/renal carcinoma antigen (for Carbonic anhydrase IX)hCAII (for human CA II)hCAIX (for human CA IX)

Reversible inhibition of the catalytic zinc active site, blocking the hydration/dehydration of CO₂. Enzyme degradation via PROTACs (for CA II). Inhibition disrupts tumor pH regulation and growth (for CA IX). Inhibition reduces aqueous humor production (glaucoma), or disrupts bicarbonate reabsorption (acidosis).