Endocrine Abstracts

Finding novel drugs and repurposing existing ones have gained increasing attention in addressing various setbacks faced by researchers in cancer research and treatment owing to the increased cancer rate, low efficacy, availability, and affordability of cancer drugs. Thus, the goal of this research is to repurpose nandrolone (ND), an inexpensive and widely available anabolic steroid, to a potential anticancer therapeutic candidate. A computer-aided drug design approach (CADD) involving virtual screening was used to obtain the binding scores (kcal/mol) and inhibiting efficiencies (IC50 µ/mol ) of ND against DNA Topoisomerase II Alpha (TOP2A), Cyclin D1, Cyclin-dependent kinases IV & VI (CDK4/6) and cancer cell lines (HEPG2, MHHNB11, SW1573, and SNU245) by employing PyRx, Pymol, Discovery studio, and PaccMann web tool. Data warrior tool and SwissADME online tool were used to conduct in silico pharmacokinetic studies involving drug-likeness and ADMET profiling of ND. The findings of these analyses were compared with the conventional (standard) cancer medicines (doxorubicin, palbociclib). Results of this study showed ND had a higher binding affinity for TOP2A, CDK4, and CDK6 with binding scores of -74kcal/mol; -5.9kcal/mol; and -9.4kcal/mol when docked into the binding pockets of three of the four proteins in comparison with that of the standards. Furthermore, it exhibited a high level of inhibitory activity against cancer cell lines with an average IC₅₀= 0.55 and demonstrated good pharmacokinetics as it possesses the required ADMET (absorption, distribution, metabolism, excretion, and toxicity) criteria. In keeping with the findings from this study, nandrolone shows promising potential as an anticancer drug candidate. However, further studies using in vitro and animal models should be conducted to elucidate the underlying mechanisms of nandrolone in combating cancer.