Identification of potential natural BCL-2 inhibitors for leukemia through an integrated virtual screening approach

Leukemia, a hematologic malignancy, frequently involves the overexpression of BCL-2 proteins, contributing to cell survival and apoptosis resistance. Although current BCL-2 inhibitors, including Venetoclax, have shown efficacy, they are limited by adverse side effects and restricted bioavailability. This study employs an integrated computational approach to identify natural BCL-2 inhibitors by screening 407,270 natural compounds. Using ligand- and structure-based virtual screening, we identified two promising compounds, CNP0237679 and CNP0420384, demonstrating strong binding affinities, favorable electronic properties, and stability in dynamic aqueous environments. Both compounds exhibited promising toxicity and pharmacokinetic profiles, indicating the possibility of low toxicity and high bioavailability. They are potential candidates for developing selective BCL-2 inhibitors because of these characteristics. The findings represent a positive step in developing new, naturally derived BCL-2 inhibitors and support additional in vitro and in vivo studies to validate their therapeutic efficacy and safety characteristics.