Cayman U-104

Carbonic anhydrases are zinc metalloenzymes that catalyze the reversible hydration of carbon dioxide to form bicarbonate ion plus a proton. Carbonic anhydrases IX (CAIX) and CAXII are hypoxia and HIF-1-inducible proteins located in cellular transmembranes that regulate intra- and extracellular pH under hypoxic conditions and promote tumor cell survival and invasion in hypoxic microenvironments. U-104 is a ureido-sulfonamide inhibitor of transmembrane CAIX (K_i = 45.1 nM) and CAXII (K_i = 4.5 nM). It demonstrates reduced affinity for the cytosolic isoforms, CAI and CAII (K_is = 5.08 and 9.64 µM, respectively). U-104 associates with CAIX/CAXII only under hypoxic conditions in vivo, reducing extracellular acidity and resulting in significant inhibition of tumor growth and metastasis in experimental models.

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