Tripartate poly(ethylene glycol) prodrugs of the open lactone form of camptothecin.
Two PEG prodrugs utilizing conjugation of PEG through the C-21 acid functionality as well as the C-17 OH group of CPT hydroxy-amide open forms were synthesized and characterized. Both of these open lactone tripartate prodrugs were shown to be water soluble and highly effective in MX-1 mouse xenograph studies. Indirect evidence implies that the initial ester or carbonate bond breaking is esterase mediated in the first step of the cascade of CPT release.
Greenwald
Richard B
RB
Enzon Inc., 20 Kingsbridge Road, Piscataway, NJ 00854, USA. richard.greenwald@enzon.com
Zhao
Hong
H
Xia
Jing
J
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology; D006207:Half-Life; D006801:Humans; D007275:Injections, Intravenous; D007783:Lactones / Q000737:chemistry*; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011092:Polyethylene Glycols / Q000737:chemistry*; D011355:Prodrugs / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D051381:Rats; D012995:Solubility
D000972:Antineoplastic Agents, Phytogenic; D007783:Lactones; D011355:Prodrugs; D011092:Polyethylene Glycols; D002166:Camptothecin