A new prodrug of paclitaxel: synthesis of Protaxel
A L Seligson1, R C Terry, J C Bressi
1Biophysica, 3333 N Torrey Pines Ct, Ste 100, La Jolla, CA 92037-1023, USA. biophysica@biophysica.net
Anti-Cancer Drugs
|May 4, 2001
Abstract:
2' and 7 Polyol carbonates of paclitaxel were synthesized and screened as potential paclitaxel prodrugs. Paclitaxel is released from 7-(2",3"-dihydroxypropylcarbonato) paclitaxel (Protaxel) at rates inversely proportional to pH, by an intramolecular cyclization. Compared to paclitaxel, maximum tolerated i.v. or i.p. doses (MTD) of Protaxel are about 2.5- to 3-fold higher; its efficacy is substantially higher in human cancer line xenografts in athymic mice, especially in prostate PC-3, breast MDA-MB 468 and ovary OVCAR-1.
