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- W3138407875 abstract "Herein we describe the design and biological evaluation of a novel antitumor therapeutic platform that combines the most favorable properties of small-molecule drug conjugates (SMDCs) and antibody drug conjugates (ADCs). Although the small size of SMDCs, compared to ADCs, is an appealing feature for their application in the treatment of solid tumors, SMDCs usually suffer from poor pharmacokinetics, which severely limits their therapeutic efficacy. To overcome this limitation, in this proof-of-concept study we grafted an α-amanitin-based SMDC that targets prostate cancer cells onto an immunoglobulin Fc domain via a two-step “program and arm” chemoenzymatic strategy. We demonstrated the superior pharmacokinetic properties and therapeutic efficacy of the resulting Fc-SMDC over the SMDC in a prostate cancer xenograft mouse model. This approach may provide a general strategy toward effective antitumor therapeutics combining small size with pharmacokinetic properties close to those of an ADC." @default.
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- W3138407875 date "2021-03-23" @default.
- W3138407875 modified "2023-10-17" @default.
- W3138407875 title "Enhancing the Pharmacokinetics and Antitumor Activity of an α-Amanitin-Based Small-Molecule Drug Conjugate via Conjugation with an Fc Domain" @default.
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- W3138407875 doi "https://doi.org/10.1021/acs.jmedchem.1c00003" @default.
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