title: A new prodrug of paclitaxel: synthesis of Protaxel.
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.
authors.affiliation: Biophysica, 3333 N Torrey Pines Ct, Ste 100, La Jolla, CA 92037-1023, USA. biophysica@biophysica.net
authors.forename: A L
authors.initials: AL
authors.lastname: Seligson
authors.forename: R C
authors.initials: RC
authors.lastname: Terry
authors.forename: J C
authors.initials: JC
authors.lastname: Bressi
authors.forename: J G
authors.initials: JG
authors.lastname: Douglass
authors.forename: M
authors.initials: M
authors.lastname: Sovak
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D001943:Breast Neoplasms / Q000188:drug therapy; D002455:Cell Division / Q000187:drug effects; D004355:Drug Stability; D004361:Drug Tolerance; D005260:Female; D006207:Half-Life; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D020714:Maximum Tolerated Dose; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010051:Ovarian Neoplasms / Q000188:drug therapy; D017239:Paclitaxel / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D011355:Prodrugs / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D011471:Prostatic Neoplasms / Q000188:drug therapy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D043823:Taxoids; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D011355:Prodrugs; D043823:Taxoids; C434865:protaxel; D017239:Paclitaxel