Synthesis and activity of a folate targeted monodisperse PEG camptothecin conjugate

[Display omitted] 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 b...

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Veröffentlicht in:	Bioorganic & medicinal chemistry letters 2013-11, Vol.23 (21), p.5810-5813
Hauptverfasser:	Henne, Walter A., Kularatne, Sumith A., Hakenjos, John, Carron, Joshua D., Henne, Kristene L.
Format:	Artikel
Sprache:	eng
Schlagworte:	Antineoplastic Agents, Phytogenic - administration & dosage Antineoplastic Agents, Phytogenic - chemistry Antineoplastic Agents, Phytogenic - pharmacokinetics Antineoplastic Agents, Phytogenic - pharmacology Camptothecin Camptothecin - administration & dosage Camptothecin - analogs & derivatives Camptothecin - pharmacokinetics Camptothecin - pharmacology chemistry cytotoxicity Drug Delivery Systems drugs Folate conjugate Folate Receptors, GPI-Anchored - metabolism folic acid Folic Acid - chemistry Humans inhibitory concentration 50 KB Cells Monodisperse PEG Neoplasms - drug therapy Neoplasms - metabolism PEG Polyethylene Glycols - chemistry Prodrugs - administration & dosage Prodrugs - chemistry Prodrugs - pharmacokinetics Prodrugs - pharmacology Small molecule drug conjugate SMDC
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Zusammenfassung:	[Display omitted] 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.
ISSN:	0960-894X 1464-3405
DOI:	10.1016/j.bmcl.2013.08.113