Network Pharmacology and Molecular Simulation Reveal Lactandrate Targeting PARP1 in Colorectal Cancer

Colorectal cancer remains a major cause of cancer mortality and the discovery of selective anticancer agents is still urgently needed. This study investigated Lactandrate as a potential anti-colorectal cancer compound by integrating network pharmacology, molecular modeling, and in silico ADMET profiling. Putative targets of Lactandrate were predicted using SwissTargetPrediction and intersected with colorectal cancer-related genes collected from GeneCards and Open Targets, yielding 104 common targets. Protein-protein interaction analysis highlighted key hub genes, including TP53, BCL2, HSP90AA1, AKT1, PARP1, BCL2L1, MCL1, MAPK3, MDM2, and MTOR. GO and KEGG enrichment suggested involvement in core oncogenic processes and pathways, notably PI3K-Akt signaling and cancer-related pathways. Molecular docking against top hub proteins indicated the strongest affinity for PARP1 (PDB: 5WS1), with Lactandrate (–11.57 kcal/mol) outperforming the reference drug Fruquintinib (–9.13 kcal/mol). A 100-ns molecular dynamics simulation supported stable Lactandrate-PARP1 binding (RMSD 0.2 nm) with persistent hydrogen bonding. pkCSM predictions indicated high intestinal absorption and favorable distribution, though potential mutagenicity warrants further validation. Overall, Lactandrate shows promise as a PARP1-targeting candidate for colorectal cancer, supporting subsequent experimental studies.