A recent study has unveiled the therapeutic potential of a compound formed through the breakdown of a cancer drug. This by-product, when combined with the original drug, exhibited a synergistic effect, inhibiting prostate cancer cells. Intriguingly, when administered alone, the compound also demonstrated the ability to reduce the accumulation of a toxic protein linked to Parkinson’s disease in the brain.
Typically, when medications are ingested, they undergo absorption and distribution throughout the body. Subsequently, they are metabolized by various organs, producing by-products known as metabolites. These metabolites, often overlooked, are present in high concentrations in the plasma and can retain pharmacological activity.
The Spanish National Research Council (CSIC) conducted a study focusing on a metabolite produced through the breakdown of the cancer drug Rucaparib. This drug is utilized for treating recurrent ovarian, breast, and prostate cancers. The major metabolite, named M324, was found to reach higher plasma concentrations in animals than the parent drug and could enter tumor cells.
Computational approaches were employed to characterize the profile of M324, identifying shared and exclusive targets with its parent drug. Subsequent experiments on lab cell lines validated the computational findings, revealing anti-cancer properties. Combining Rucaparib and M324 showed increased inhibition of cancer cells, particularly in prostate cancer cell lines, where the synergistic effect surpassed 30%.
Moving beyond cancer, the researchers explored the impact on Parkinson’s disease. Treating dopamine neurons associated with Parkinson’s with M324 effectively reduced the accumulation of ⍺-synuclein, a protein implicated in the development of the disease.
The study’s implications extend to clinical impact, suggesting that the synergistic effect observed in prostate cancer could influence advanced-stage clinical trials. Additionally, the findings raise considerations about the safety and efficacy of the drug combination. Regarding Parkinson’s disease, the study opens up the possibility of repurposing the metabolite as a novel therapeutic approach.
In conclusion, the researchers emphasize the significance of understanding the distinct polypharmacology of drug metabolites compared to their parent drugs. They advocate for making drug metabolites commercially available, incorporating them in preclinical studies, and thoroughly characterizing them during drug development to tailor precision medicine and enhance clinical outcomes.
