Rational structure-guided identification of a Bcl-2-targeting peptide with antiproliferative effects on colorectal cancer cells.

Authors

Xing Jin, Shudan Yang, Qianqian Wang, Shutong Chen, Yi-Nan Wang, Yang Yang

Published in

Journal of enzyme inhibition and medicinal chemistry. Volume 41. Issue 1. Pages 2747402. Epub Oct 14, 2026.

Abstract

Bcl-2 is critical for tumour survival and serves as a promising anticancer drug target. Herein, a series of novel Bcl-2-targeted peptides were identified through structure-based virtual screening and systematic biological validation. Four candidate peptides were selected from the peptide library. MST results demonstrated that Peptide 1 exhibited the strongest apparent binding affinity towards Bcl-2 (K_d = 0.51 ± 0.03 μM), superior to VS-9 and other screened peptides. Molecular dynamics simulation, free energy landscape analysis, and MM/GBSA calculation further supported the predicted conformational features of the Bcl-2-Peptide-1 complex. MTT assays demonstrated that Peptide-1 markedly inhibited the proliferation of HT29 and Colo320HSR colorectal cancer cells, while showing limited effects on normal NCM460 cells. Bcl-2 knockdown attenuated the bioactivity of Peptide-1, and RT-qPCR and ELISA analyses revealed that Peptide-1 modulated Bax/Bcl-2 expression at both transcriptional and protein levels. Peptide-1 represents a promising Bcl-2-targeting peptide with antiproliferative activity against colorectal cancer cells.

PMID:
42875898
Bibliographic data and abstract were imported from PubMed on 15 Oct 2026.

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