title: Targeting carbonic anhydrase IX with small organic ligands.
abstract: Carbonic anhydrase IX (CAIX) is expressed in many solid tumors in response to hypoxia and plays an important role in tumor acid-base homeostasis under these conditions. It is also constitutively expressed in the majority of renal cell carcinoma. Its functional inhibition with small molecules has recently been shown to retard tumor growth in murine models of cancer, reduce metastasis and tumor stem cell expansion. Additionally, CAIX is a promising antigen for targeted drug delivery approaches. Initially validated with anti-CAIX antibodies, the tumor-homing capacity of high-affinity small-molecule ligands of CAIX has recently been demonstrated. Indeed, conjugates formed of CAIX ligands and potent cytotoxic drugs could eradicate CAIX-expressing solid tumors in mice. These results suggest that CAIX is a promising target for the development of novel therapies for the treatment of solid tumors.
authors.affiliation: ETH Zurich, Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, 8093 Zurich, Switzerland.
authors.forename: Moreno
authors.initials: M
authors.lastname: Wichert
authors.affiliation: ETH Zurich, Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, 8093 Zurich, Switzerland. Electronic address: nikolaus.krall@pharma.ethz.ch.
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Krall
mesh_terms: D000086:Acetazolamide / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D000951:Antigens, Neoplasm / Q000737:chemistry* / Q000378:metabolism; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D000071231:Carbonic Anhydrase IX; D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D002256:Carbonic Anhydrases / Q000737:chemistry* / Q000378:metabolism; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D006801:Humans; D008024:Ligands; D051379:Mice; D058990:Molecular Targeted Therapy; D055503:Protein Multimerization; D054852:Small Molecule Libraries / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D002257:Carbonic Anhydrase Inhibitors; D008024:Ligands; D054852:Small Molecule Libraries; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases; D000086:Acetazolamide