Synthesis and in vivo antitumor activity of poly(l-glutamic acid) conjugates of 20S-camptothecin.
Poly-alpha-(l-glutamic acid) (PG) conjugates of 20(S)-camptothecin (1, CPT) displayed improved aqueous solubility compared to CPT, were stable in aqueous solution at neutral pH, and were potent antitumor agents in vivo. Evaluation of PG molecular weight, CPT loading, aqueous solubility, and CPT equivalent dosing with respect to in vivo antitumor potencies of various linked conjugates led to identification of a preferred conjugate composition.
Bhatt
Rama
R
Cell Therapeutics, Inc., 201 Elliott Avenue West, Seattle, Washington 98119, USA.
de Vries
Peter
P
Tulinsky
John
J
Bellamy
Garland
G
Baker
Brian
B
Singer
Jack W
JW
Klein
Peter
P
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D004355:Drug Stability; D006863:Hydrogen-Ion Concentration; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D011099:Polyglutamic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D012996:Solutions; D013329:Structure-Activity Relationship; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D012996:Solutions; D011099:Polyglutamic Acid; D002166:Camptothecin