title: Selective carbonic anhydrase IX inhibitors based on coumarin scaffold as promising antimetastatic agents: WO2012070024.
abstract: 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.
authors: Sapienza University of Rome, Department of Drug Chemistry and Technologies, P.le A. Moro 5, 00185 Rome, Italy. simone.carradori@uniroma1.it
authors: Simone
authors: S
authors: Carradori
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000187:drug effects / Q000378:metabolism; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D000071231:Carbonic Anhydrase IX; D002257:Carbonic Anhydrase Inhibitors / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D002256:Carbonic Anhydrases / Q000187:drug effects / Q000378:metabolism; D002448:Cell Adhesion; D015687:Cell Hypoxia; D003374:Coumarins / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D006801:Humans; D006863:Hydrogen-Ion Concentration; D051379:Mice; D058990:Molecular Targeted Therapy; D009362:Neoplasm Metastasis / Q000517:prevention & control; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010330:Patents as Topic
chemical_list: D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D002257:Carbonic Anhydrase Inhibitors; D003374:Coumarins; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases