Design, synthesis and anticancer evaluation of novel oncolytic peptide-chlorambucil conjugates

Yin, Hao; Fu, Xing-Yan; Gao, Hanyu; Ma, Yan-Nan; Du, Shanshan; Qi, Yun‐Kun; Wang, Kewei

doi:10.1016/j.bioorg.2023.106674

Cited by 6 publications

(2 citation statements)

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“…Except for disrupting the integrity of cancer cell membranes, oncolytic peptides were demonstrated to destroy the intracellular membrane especially the mitochondrial membrane, the combination of which induced the rapid death of cancer cells. ,− The subcellular localization suggested that FXY-12 could rapidly penetrate the cell membrane and efficiently aggregate in the mitochondria from 10 to 120 min. Therefore, the damaging effect of LTX-315 and FXY-12 on the mitochondria was investigated, and the JC-10 detection kit was applied to monitor the changes in mitochondrial membrane potential (MMP, Figure B,D).…”

Section: Resultsmentioning

confidence: 99%

“…Inspired by the PDC strategy, we chose cytotoxic drugs as warheads and added cytotoxic drugs to oncolytic peptides, aiming to improve the anticancer potential of traditional oncolytic peptides. ,,, Considering the wide spectrum anticancer potency, we chose the chemotherapeutic drug CPT as the warhead in this study . The CPT, isolated from the stem and bark of the Chinese tree, Camptotheca acuminata, is a cytotoxic alkaloid that attenuates the replication of cancer cells through inhibiting DNA topoisomerase I .…”

Section: Resultsmentioning

confidence: 99%

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Three Rounds of Stability-Guided Optimization and Systematical Evaluation of Oncolytic Peptide LTX-315

Fu,

Yin,

Chen

et al. 2024

J. Med. Chem.

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Oncolytic peptides represent promising novel candidates for anticancer treatments. In our efforts to develop oncolytic peptides possessing both high protease stability and durable anticancer efficiency, three rounds of optimization were conducted on the first-in-class oncolytic peptide LTX-315. The robust synthetic method, in vitro and in vivo anticancer activity, and anticancer mechanism were investigated. The D-type peptides represented by FXY-12 possessed significantly improved proteolytic stability and sustained anticancer efficiency. Strikingly, the novel hybrid peptide FXY-30, containing one FXY-12 and two camptothecin moieties, exhibited the most potent in vitro and in vivo anticancer activities. The mechanism explorations indicated that FXY-30 exhibited rapid membranolytic effects and induced severe DNA double-strand breaks to trigger cell apoptosis. Collectively, this study not only established robust strategies to improve the stability and anticancer potential of oncolytic peptides but also provided valuable references for the future development of D-type peptides-based hybrid anticancer chemotherapeutics.

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