Aspirin Redesigned: A CADD-Guided Exploration of Optimized Aspirin Analogs for Targeted Cancer Therapy

This study unveils the remarkable potential of repurposing aspirin, a widely available and well-tolerated drug, for targeting the beta-catenin pathway in cancer therapy. Leveraging computer-aided drug design (CADD) techniques, we embarked on an in silico exploration that identified a library of potent aspirin analogs exhibiting significantly enhanced binding affinity and selectivity towards beta-catenin. Molecular dynamics simulations predicted robust and long-lasting analog-beta-catenin complexes, implying sustained inhibition of beta-catenin activity. Comprehensive in silico screening revealed minimal off-target interactions, mitigating potential side effects. In silico ADMET profiling identified candidates with favorable pharmacokinetic properties for advancement to preclinical and clinical trials. Through rigorous prioritization, we generated a ranked list of promising analogs, including diaspirin, fumaryl diaspirin, PN511, PN512, PN524, and PN525. This research establishes a framework for accelerated drug repurposing, contributing to precision medicine and affordable cancer treatment strategies