Antitumor activity of paclitaxel-2'-glycinate conjugated to poly(ethylene glycol): a water-soluble prodrug.
Synthesis and in vivo antitumor activity evaluation of water-soluble poly(ethylene glycol) (PEG)-conjugated paclitaxel-2'-glycinate (6) are reported. This prodrug demonstrated enhanced antitumor activity and less toxicity in a P388/0 murine leukemia model when compared, on an equimolar basis, with native paclitaxel formulated in Cremophor/ethanol. Employing 6 in the treatment of HT-29, A549 and SKOV3 solid tumor-bearing xenografted mice demonstrated significant antitumor activity. The outstanding performance of 6 may be attributed partly to the tripartate nature of the prodrug.
Enzon Inc., Piscataway, NJ 08854-3969, USA.
A
A
Pendri
C D
CD
Conover
R B
RB
Greenwald
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D002470:Cell Survival / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D005079:Excipients / Q000737:chemistry; D006801:Humans; D007202:Indicators and Reagents; D007941:Leukemia P388 / Q000188:drug therapy; D051379:Mice; D009368:Neoplasm Transplantation; D017239:Paclitaxel / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000633:toxicity; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D011355:Prodrugs; D043823:Taxoids; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D000972:Antineoplastic Agents, Phytogenic; D005079:Excipients; D007202:Indicators and Reagents; D011355:Prodrugs; D043823:Taxoids; C113924:poly(ethylene glycol)-conjugated paclitaxel-2'-glycinate; D011092:Polyethylene Glycols; D017239:Paclitaxel