polyethyleneglycol-7-ethyl-10-hydroxycamptothecin DFP-13318

A long-acting formulation composed of 7-ethyl-10-hydroxycamptothecin (SN38), a camptothecin derivative and active metabolite of irinotecan conjugated to polyethylene glycol (PEG), via a proprietary, cleavable linker, with potential antineoplastic activity. Upon administration, the proprietary linkage system allows for very slow release of SN38 from the formulation. Upon release, SN38 selectively stabilizes covalent topoisomerase I-DNA complexes, and results in single-stranded and double-stranded DNA breaks, the inhibition of DNA replication, and the induction of apoptosis. This agent is designed to deliver the active metabolite to tumor cells without the need for conversion as is the case with irinotecan. Compared to other PEG-SN38-based formulations, the linker system in DFP-13318 increases its half-life and the exposure time for tumor cells, while decreasing both blood plasma concentrations and exposure to off-target organs; this results in increased efficacy.