Synthesis and activity of a folate targeted monodisperse PEG camptothecin conjugate.
A folate targeted camptothecin small molecule drug conjugate (SMDC) was synthesized using a monodisperse PEG spacer linked to folate via a releasable disulfide carbonate linker. Cell cytotoxicity in human KB cells exhibited an IC50 of 6nM. Importantly, activity of the prodrug was blocked by excess folate, demonstrating receptor-mediated celluar uptake of the PEG conjugate.
Division of Science, Governors State University, 1 University Parkway, University Park, IL 60484, USA. Electronic address: whenne@govst.edu.
Walter A
WA
Henne
Sumith A
SA
Kularatne
John
J
Hakenjos
Joshua D
JD
Carron
Kristene L
KL
Henne
D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D016503:Drug Delivery Systems; D058973:Folate Receptors, GPI-Anchored / Q000378:metabolism; D005492:Folic Acid / Q000737:chemistry*; D006801:Humans; D007624:KB Cells; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D011092:Polyethylene Glycols / Q000737:chemistry*; D011355:Prodrugs / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology
D000972:Antineoplastic Agents, Phytogenic; D058973:Folate Receptors, GPI-Anchored; D011355:Prodrugs; D011092:Polyethylene Glycols; D005492:Folic Acid; D002166:Camptothecin
Camptothecin; Folate conjugate; Monodisperse PEG; PEG; SMDC; Small molecule drug conjugate