Integrated virtual screening and in vitro evaluation identify potential c-Myc/max complex inhibitors for colorectal cancer
Year: 2026
Type: article
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.
Source: Results in Chemistry
Language: English
Subfield: Drug Discovery
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $1,870
OpenAlex ID: W7222823732