Integrated virtual screening and in vitro evaluation identify potential c-Myc/max complex inhibitors for colorectal cancer
- 1Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China; Department of General Surgery, Yancheng Third People's Hospital, The Sixth Affiliated Hospital of Nantong University, Yancheng, 224000, China
- 2Department of General Surgery, Yancheng Third People's Hospital, The Sixth Affiliated Hospital of Nantong University, Yancheng, 224000, China
- 3Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China; Corresponding author.
Abstract
c-Myc, a key oncogene driving aggressive colorectal cancer (CRC), forms a heterodimer with transcription factor Max. This c-Myc–Max complex binds the conserved E -box sequence (CACGTG) to regulate target gene transcription. Disrupting c-Myc/Max dimerization thus represents a promising strategy to suppress c-Myc oncogenic activity. This study screened the ChemDiv library via structure-based virtual screening targeting the c-Myc/Max complex, followed by cellular evaluation of candidate compounds in CRC cell lines. Four compounds, 6069–0336, C201–1652, D144–0281, and E959–1030, were identified via structure-based virtual screening. Among these candidates, D144–0281 and E959–1030 were found to potentially suppress CRC cell viability, induce apoptosis, and downregulate c-Myc protein expression without affecting its mRNA transcription. Luciferase reporter assays and GST pull-down assays confirmed that the two compounds inhibit c-Myc transcriptional activity and disrupt c-Myc–Max binding. Molecular dynamics (MD) simulations and MM/GBSA binding free energy calculations further verified their strong binding affinity to the target and revealed their distinct interaction mechanisms. Compounds D144–0281 and E959–1030 are promising c-Myc/Max interaction inhibitors that warrant further investigation into their action mechanisms and in vivo anti-CRC activity evaluation.
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BibTeX
@article{miao2026integrated,
title = {{Integrated virtual screening and in vitro evaluation identify potential c-Myc/max complex inhibitors for colorectal cancer}},
author = {Zhilong Miao and Guokan Ge and Aishan Chen and Xiaobing Liu and Yuting Kuang and Hengfeng Cui},
journal = {Results in Chemistry},
year = {2026},
month = oct,
doi = {10.1016/j.rechem.2026.103982},
url = {https://doi.org/10.1016/j.rechem.2026.103982},
note = {CC BY},
}
RIS
TY - JOUR
TI - Integrated virtual screening and in vitro evaluation identify potential c-Myc/max complex inhibitors for colorectal cancer
AU - Zhilong Miao
AU - Guokan Ge
AU - Aishan Chen
AU - Xiaobing Liu
AU - Yuting Kuang
AU - Hengfeng Cui
PY - 2026
DA - 2026/10/30
JO - Results in Chemistry
DO - 10.1016/j.rechem.2026.103982
UR - https://doi.org/10.1016/j.rechem.2026.103982
AB - c-Myc, a key oncogene driving aggressive colorectal cancer (CRC), forms a heterodimer with transcription factor Max. This c-Myc–Max complex binds the conserved E -box sequence (CACGTG) to regulate target gene transcription. Disrupting c-Myc/Max dimerization thus represents a promising strategy to suppress c-Myc oncogenic activity. This study screened the ChemDiv library via structure-based virtual screening targeting the c-Myc/Max complex, followed by cellular evaluation of candidate compounds in CRC cell lines. Four compounds, 6069–0336, C201–1652, D144–0281, and E959–1030, were identified via structure-based virtual screening. Among these candidates, D144–0281 and E959–1030 were found to potentially suppress CRC cell viability, induce apoptosis, and downregulate c-Myc protein expression without affecting its mRNA transcription. Luciferase reporter assays and GST pull-down assays confirmed that the two compounds inhibit c-Myc transcriptional activity and disrupt c-Myc–Max binding. Molecular dynamics (MD) simulations and MM/GBSA binding free energy calculations further verified their strong binding affinity to the target and revealed their distinct interaction mechanisms. Compounds D144–0281 and E959–1030 are promising c-Myc/Max interaction inhibitors that warrant further investigation into their action mechanisms and in vivo anti-CRC activity evaluation.
SN - 2211-7156
ER -