Background: Brain cancer from metastasized breast cancer has a high mortality rate in
women. The treatment of lesions is hampered in large part by the blood-brain barrier (BBB), which
prevents adequate distribution of anti-cancer compounds to brain metastases.
Method: In this study we used a novel screening method to identify candidate molecules that are
well-suited to utilizing the BBB choline transporter for distribution into the brain parenchyma.
Results: From our screen we identified two compounds, Ch-1 and Ch-2 that were able to reduce the
brain tumor burden in a murine mouse model of brain metastasis of breast cancer. These compounds
also significantly increased the survival of mice by more than 10 days. Mechanistic studies indicated
that Ch-1 is able to prevent the activation of the pro-survival mitogen-activated kinases (MAPKs) by
osteoactivin (OA; Glycoprotein nonmetastatic melanoma protein B GPNMB).
Conclusion: The results from this study show that nutrient transporter virtual screening is a viable
novel alternative to traditional drug screening programs to identify anti-cancer compounds for the
treatment of brain cancers.