Antitumour activity of DX-8951f: a new camptothecin derivative
| Autor: | Eiji Kumazawa, Akiko Tohgo |
|---|---|
| Rok vydání: | 1998 |
| Předmět: | |
| Zdroj: | Expert Opinion on Investigational Drugs. 7:625-632 |
| ISSN: | 1744-7658 1354-3784 |
| Popis: | DX-8951f is a water-soluble camptothecin analogue with a unique hexacyclic structure. Compared to other current camptothecin derivatives, DX-8951f is the most effective topoisomerase I (topo I) inhibitor and has the most potent cytotoxic activity against various tumour cell lines in vitro. Of particular interest is DX-8951f's significant effect on certain tumour cell lines resistant to other camptothecin derivatives, as well as on multi-drug resistant variants that overexpress P-glycoprotein. In addition, in in vivo xenograft systems using nude mice, DX-8951f strongly inhibits the growth of human solid tumours, including resistant tumours. Its antitumour effects and resulting life prolongation in tumour-bearing mice have also been confirmed in several metastasis models. DX-8951f provides greater therapeutic efficacy and broader effective dose ranges using multiple injections than with a bolus injection and simple intermittent applications. The in vivo effects of the compound are superior to those of CPT-11 and SKF104864, suggesting that DX-8951f is a promising therapeutic agent for the treatment of cancer patients. Phase I clinical trials are ongoing in Europe, the USA and Japan. |
| Databáze: | OpenAIRE |
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