JKYN-1

JKYN-1 is a small-molecule inhibitor of the RAD51 recombinase, a key protein in homologous recombination-mediated double-strand DNA break repair and replication stress tolerance. Discovered through virtual chemical modifications of the earlier inhibitor IBR120, JKYN-1 exhibits improved solubility and potency. In preclinical models of non-small cell lung cancer (NSCLC), including patient-derived organoids, JKYN-1 has demonstrated significant cytotoxicity as a single agent and synergistic activity when combined with the EGFR inhibitor osimertinib, particularly in osimertinib-resistant models. It works by binding to and destabilizing RAD51, leading to its downregulation.