Traditional chemotherapeutics used in cancer therapy do not preferentially accumulate in tumor tissues. The conjugation to delivery vehicles like antibodies or small molecules has been proposed as a strategy to increase the tumor uptake and improve the therapeutic window of these drugs. Here, we report the synthesis and the biological evaluation of a novel small molecule-drug conjugate (SMDC) comprising a high-affinity bidentate acetazolamide derivative, targeting carbonic anhydrase IX (CAIX), and cryptophycin, a potent microtubule destabilizer. The biological activity of the novel SMDC was evaluated in vitro, measuring binding to the CAIX antigen by surface plasmon resonance and cytotoxicity against SKRC-52 cells. In vivo studies showed a delayed growth of tumors in nude mice bearing SKRC-52 renal cell carcinomas.
ACS omega. 2018 Nov 02 [Epub]
Samuele Cazzamalli, Eduard Figueras, Lilla Pethő, Adina Borbély, Christian Steinkühler, Dario Neri, Norbert Sewald
Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology (ETH Zürich), Vladimir-Prelog-Weg 4, CH-8093 Zürich, Switzerland., Department of Chemistry, Organic and Bioorganic Chemistry, Bielefeld University, Universitätsstraße 25, D-33615 Bielefeld, Germany., Exiris s.r.l., Via Savona 6, I-00182 Rome, Italy.