KT-300

KT-300 is a potent and selective small-molecule inhibitor of the E3 ubiquitin ligase TRIM7, developed by Kayak Therapeutics in collaboration with Shattuck Labs and R2M Pharma. TRIM7 is a downstream effector in the RTK-KRAS pathway that is upregulated in KRAS-mutant and MSI-high tumors. Its hyperactivation leads to the stabilization of RACO-1, which activates cJun/AP1 transcription to drive cell proliferation, and the degradation of MAVS and STING, which impairs innate immune signaling. KT-300 disrupts these processes, reducing tumor growth and restoring STING-mediated interferon responsiveness. It has shown efficacy in various KRAS/NRAS mutant models, including non-small cell lung cancer (NSCLC), colorectal cancer (CRC), and pancreatic ductal adenocarcinoma (PDAC), and may address resistance to existing KRAS inhibitors.