Projects include:
- KLF5 inhibitors for colorectal cancer therapy.
- TBK1 and IKKi dual kinase inhibitors, for hormone-refractory prostate cancer.
- Inhibitors of kinases CK1delta, ASK1, and ULK1, for various cancers.
- Modulators of the HIPPO-YAP pathway, for various cancers.
Our cancer projects target unique metabolic phenotypes of tumor cells, identifying defining molecular characteristics to be exploited for the development of targeted therapies. Most tumor types have a shared reliance upon active transport of nutrients and building blocks to drive rapid cancer cell growth and to sustain survival. They also largely rely upon glycolysis for ATP production (the Warburg effect). As examples, we have created molecules to keep tumor cells from exporting lactate, the end product of glycolysis. We have also designed compounds to block amino acid transporters that are up-regulated by many tumors. We have a program targeting expression of a transcription factor that drives colon cancer progression. We also have a number of kinase inhibitor programs aimed at the discovery of treatments for brain cancers, triple-negative breast cancer, hormone-resistant prostate cancer, and perhaps other forms as well. These are collaborative efforts with top TSRI cancer biologists including Derek Duckett, Joseph Kissil, Jun-li Luo, and also including John Cleveland from the Moffitt Cancer Center.
Many of our anticancer programs have a computational chemistry-directed focus, relying on molecular modeling based upon published coordinates, virtual screening, scoring, and validation of predicted hits through chemical synthesis. We use the Schrodinger suite of modeling software in these studies. For future work we may have a need to hire postdoctoral scientists with both computational and synthesis experience. Please contact me for further information.
