Federal Project Grant Award Summary

The National Institute of General Medical Sciences (NIGMS) awarded The Johns Hopkins University a $559,800 Project Grant (CFDA 93.859: Biomedical Research and Research Training) effective July 1, 2026 through March 31, 2031 to develop rapafucins—novel macrocyclic compounds designed as chemical probes and potential drug leads for "undruggable" protein targets. The research focuses on mechanistic investigation and structural optimization of four rapafucin leads: rapaprotin (a proteasome inhibitor demonstrating synergy with clinical agents such as bortezomib), rapanfatin and rapafosin (transcription factor inhibitors targeting NFAT and c-fos, respectively), and rapayapon (a YAP coactivator activator with regenerative applications). These activities build upon a 45,000-compound rapafucin library generated by combining rapamycin's FKBP-binding domain with a combinatorial tetrapeptide library.

The grant supports discovery chemistry and chemical biology research that addresses a fundamental challenge in drug development—targeting protein-protein interactions occurring intracellularly where traditional small molecules are ineffective. Successful completion of this project will yield new chemical probes and drug candidates with therapeutic implications across multiple human disease areas. The work is performed at Johns Hopkins University's Baltimore, Maryland facility.