Abstract 196P
Background
Management of breast cancer has significantly changed in the last few years, witnessing the advent of more and more therapeutic approaches. Female breast cancer has surpassed lung cancer as the most commonly diagnosed cancer, with an estimated 2.3 million new cases according to GLOBOCAN, 2020. With the significant increase in the incidence of breast cancer, targeted therapies are in urgent need for treatment. Aberrantly high levels of Estrogen Receptor alpha (ESR1) are found in more than 70% of all breast cancers and found to be a crucial therapeutic target for treating ESR1 positive breast cancer. A systematic in silico study was carried out to find out some potential statin drug candidates that may be used in breast cancer treatment.
Methods
Molecular docking of statins and the reference drug (brilanestrant) with ESR1, superimposition of selected drugs with ESR1-reference, comparison of interactions of reference and candidate drugs with the protein (ESR1) and pharmacokinetic properties of the chosen drugs were evaluated to come up with the most promising statin drug candidate for breast cancer treatment. Targeting ESR1, screening of statin drugs was carried out via several in silico approaches.
Results
Brilanestrant had a binding affinity of -8.6 kcal/mol. The drugs with the highest binding affinities were then superimposed with the reference. Based on the superimposition results, drug-protein interactions were visualized in Discovery Studio. Among them, pitavastatin, rosuvastatin and simvastatin had four common amino acids with the ESR1-reference interactions. The pharmacokinetic properties of both the reference and selected candidates were assessed using QikProp. The predicted human oral absorption of brilanestrant was 79.35%. Simvastatin, lovastatin and mevastatin showed excellent human oral absorption (100%). They also showed excellent intestinal permeability compared to the reference and did not penetrate the CNS or the blood brain barrier as suggested by the CNS, logBB and PSA values.
Conclusions
The study indicates that the drugs, simvastatin, lovastatin and mevastatin could be effective drugs in breast cancer treatment. However, further studies including in vitro and in vivo tests will be required to investigate their safety, efficacy and dosing profiles.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.