Federal Grant Award Summary

The University of Southern California received a $680,452 Project Grant award from the National Cancer Institute under the Cancer Treatment Research program (CFDA 93.395), effective June 9, 2026, with a completion date of May 31, 2029. This research initiative focuses on discovering novel small-molecule compounds that selectively target the BMAL1:CLOCK circadian regulatory complex for cancer therapeutic applications. The project addresses a significant gap in drug discovery by developing a comprehensive screening pipeline that combines affinity selection mass spectrometry (AS-MS) binding assays with cell-based HIBIT reporter assays to identify and validate compounds that can modulate circadian clock proteins implicated in glioblastoma, acute myeloid leukemia, and hepatocellular carcinoma.

The deliverables include conducting a large-scale high-throughput screening campaign to identify hit compounds from the refined pipeline, followed by rigorous hit validation and structure-activity relationship analysis. Through integrated cheminformatics analysis and medicinal chemistry optimization, the project will advance promising lead compounds toward potential cancer therapeutic development. This research builds upon preliminary pilot screening results that identified two selective small molecules targeting BMAL1 and CLOCK, respectively, providing a foundation for the expanded screening and optimization activities funded through this award.