Dr. Wei Li

Title: "The discoveries of brain penetrable tubulin inhibitors for breast cancer brain metastasis and selective TRPC3 inhibitors for epilepsy"

Short summary of the presentation:

Breast cancer brain metastasis (BCBM) remains a clinical challenge marked by limited therapeutic options and poor survival rates. We developed a set of colchicine binding site inhibitors (CBSIs) targeting tubulin, that show potent preclinical efficacy against brain and extracranial metastases in BCBM models. These compounds efficiently cross the BBB with high brain/plasma ratios, extend overall survival and suppress the expansion of pre-established brain lesions. In the second part of the talk, I will discuss our recent efforts in developing selective transient receptor potential canonical 3 (TRPC3) inhibitors for epilepsy. Perturbation in the expression of TRPC3 are associated with several pathophysiological conditions responsible for disorders of cardiovascular, immune, and central nervous systems. While there are several reported TRPC3 inhibitors, most of them either have low inhibition potency or are not selective for TRPC3. Collaborating with biologists, we discovered new sets of metabolically stable and low-toxic TRPC3 inhibitors with good brain penetrations. These compounds are being evaluated in epilepsy and potentially other diseases.