The National Cancer Institute (NCI) awarded a $1,305,116 Project Grant under the Cancer Treatment Research program (CFDA 93.395) to the University of Pittsburgh to conduct a high-throughput screening campaign to identify novel allosteric inhibitors of the tyrosine kinase BTK. The goal is to develop new drugs that can block BTK signaling and potentially overcome resistance mechanisms associated with existing BTK inhibitors used to treat B-cell malignancies like chronic lymphocytic leukemia. The university will leverage its expertise in TEC family kinase biology, high-content screening, pharmacology, and medicinal chemistry to validate hit compounds that disrupt BTK dimerization and activation. Successful completion of this 3-year research project is expected to yield small molecule leads that can suppress the emergence of resistance mutations, enhancing the efficacy of BTK-targeted therapies.
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