U-104

U-104 is a ureido-sulfonamide inhibitor of transmembrane carbonic anhydrase IX (CAIX) (Ki = 45.1 nM) and XII (CAXII) (Ki = 4.5 nM). It displays weaker affinity for the cytosolic isoforms, CAI and CAII (Kis = 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.