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Tasidotin Hydrochloride
Tasidotin HCl (tasidotin) is a novel, third generation, synthetic, water-soluble, dolastatin pentapeptide analog of dolastatin 15. Tasidotin is metabolically stable and orally bioavailable.
Tasidotin has a unique mechanism of action that appears to differ from other microtubule stabilizers such as taxanes and epothilones and tubulin inhibitors such as Vinca alkaloids. Mechanistically, tasidotin is believed to inhibit cell proliferation by suppressing spindle microtubule dynamics through a reduction of the shortening rate, reduction of the switching frequency from growth to shortening and reduction of the time microtubules grow.
Three Phase I dose-escalation studies have been conducted to evaluate tasidotin in adult patients with metastatic or inoperable solid tumors for which no standard therapy existed or that had progressed or recurred following standard therapy.
Phase II studies have been conducted in the following populations to further evaluate the efficacy of tasidotin administered intravenously (IV): melanoma, non-small cell lung cancer, and hormone-refractory prostate cancer.
Overall, tasidotin (IV) was well tolerated, but did not show sufficient efficacy to warrant further single agent development using this route of administration.
Tasidotin will be investigated as an orally administered antineoplastic agent (as the hydrochloride salt) for patients with advanced, refractory neoplasms based on new preclinical data