Timeframe: 2025 – 2027
Goal: Investigate ways to therapeutically target DNAJ-PKAc
Principal Investigators: Rafael Couñago, PhD and David Drewry, PhD
Study overview: Small-molecule inhibitors of protein kinases have transformed cancer research by improving survival rates and enabling more targeted therapies. This progress stems from the fact that many cancers exhibit dysregulated protein kinases. When these kinases become overactive—through changes like mutations or abnormal fusions—they can fuel cancer growth. Fibrolamellar Carcinoma (FLC) is driven by one such abnormal fusion called DNAJ-PKAc. This effort is focused on finding new drugs that specifically block this fusion protein, cutting off a key driver of the disease.
This project is led by Drs. Rafael Couñago and David Drewry at UNC, both principal investigators within the Structural Genomics Consortium (SGC)—a global public-private partnership committed to advancing drug discovery through open science. Dr. Couñago brings expertise in protein biochemistry, crystallography, and assay development, while Dr. Drewry is a medicinal chemistry specialist with a strong track record in discovering selective compounds. In this project, they will evaluate several candidate compounds for selective binding to the fusion kinase, test these compounds in biochemical assays, and apply iterative medicinal chemistry to optimize them for subsequent evaluation in FLC models.
The ultimate goal of the effort is to identify new, targeted therapies for young people battling this devastating cancer.