Discovering Covalent Ligand Inhibitors for Cancer-Driving Mutations
Currently, most chemotherapy drugs used for cancer treatment target specific upregulated or dysfunctional pathways, rather than specific cancer-driving mutations. This results in adverse side effects or reduced applicability, since the drug can also affect normal pathways of healthy cells. In many tumors, cancer-driving mutations alter amino acid residues into cysteines. Due to cysteine’s unique chemical properties, these mutations are an ideal target for covalently binding molecules. This approach is especially useful in undruggable proteins lacking traditionally targeted binding pockets. In this regard, the Nomura Research Group has applied target-based screening of its cysteine-reactive compound library to identify hit compounds that covalently bind target proteins. In this project, I will express, purify, and screen human proteins with common cancer-driving mutations. Subsequently, I intend to utilize established chemoproteomic platforms to characterize hit features like proteome-wide selectivity and on-target engagement. My project ultimately intends to identify and characterize therapeutically useful chemical compounds targeting specific cancer-driving mutations.
Message to Sponsor
- Major: Chemical Biology
- Sponsor: Rose Hills Foundation
- Mentor: Daniel Nomura