Sapienza University of Rome, Department of Drug Chemistry and Technologies, P.le A. Moro 5, 00185 Rome, Italy.
Expert Opin Ther Pat. 2013;23(6):751-6. doi: 10.1517/13543776.2013.769523. Epub 2013 Feb 7.
Human carbonic anhydrase (hCA) IX is involved in tumorigenesis and metastasis through pathways modulating extracellular pH regulation and cell adhesion control. As a consequence, hCA IX represents a promising antitumor target for the development of new drugs in order to treat/image hypoxic cancers, and different agents targeting hCA IX are currently in Phase I - III clinical trials. Among novel chemotypes, coumarins and their congeners were shown to be potent and selective hCA IX inhibitors (CAI) in vitro with an alternative mechanism of action in respect to sulfonamide-based inhibitors. Furthermore, treatment of mice harboring CA IX-positive 4T1 mammary tumors with these selective coumarin-based CA IX inhibitors resulted in significant reduction of tumor growth and metastasis formation in both spontaneous and experimental models of metastasis.
人碳酸酐酶（hCA）IX 通过调节细胞外 pH 值调节和细胞黏附控制的途径参与肿瘤发生和转移。因此，hCA IX 代表了一个有前途的抗肿瘤靶标，可用于开发新的药物来治疗/成像缺氧癌症，目前有不同针对 hCA IX 的药物处于 I 期-III 期临床试验。在新型化学类型中，香豆素及其同系物被证明是体外具有强大和选择性的 hCA IX 抑制剂（CAI），与基于磺胺的抑制剂的作用机制不同。此外，用这些选择性香豆素基 CA IX 抑制剂治疗携带有 CA IX 阳性 4T1 乳腺肿瘤的小鼠，在自发和实验转移模型中均导致肿瘤生长和转移形成的显著减少。
