In Vivo Antitumor Activity of a Novel Acetazolamide-Cryptophycin Conjugate for the Treatment of Renal Cell Carcinomas.
- Cazzamalli S Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology (ETH Zürich), Vladimir-Prelog-Weg 4, CH-8093 Zürich, Switzerland.
- Figueras E Department of Chemistry, Organic and Bioorganic Chemistry, Bielefeld University, Universitätsstraße 25, D-33615 Bielefeld, Germany.
- Pethő L Department of Chemistry, Organic and Bioorganic Chemistry, Bielefeld University, Universitätsstraße 25, D-33615 Bielefeld, Germany.
- Borbély A Department of Chemistry, Organic and Bioorganic Chemistry, Bielefeld University, Universitätsstraße 25, D-33615 Bielefeld, Germany.
- Steinkühler C Exiris s.r.l., Via Savona 6, I-00182 Rome, Italy.
- Neri D Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology (ETH Zürich), Vladimir-Prelog-Weg 4, CH-8093 Zürich, Switzerland.
- Sewald N Department of Chemistry, Organic and Bioorganic Chemistry, Bielefeld University, Universitätsstraße 25, D-33615 Bielefeld, Germany.
- 2018-12-12
Published in:
- ACS omega. - 2018
English
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.
- Language
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- English
- Open access status
- gold
- Identifiers
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- DOI 10.1021/acsomega.8b02350
- PMID 30533574
- Persistent URL
- https://sonar.ch/global/documents/140032
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