SC3499

SC3499 (also known as IN-207375) is an orally active, allosteric bifunctional degrader (PROTAC) designed to selectively target and eliminate mutant epidermal growth factor receptor (EGFR) proteins, specifically those harboring the L858R mutation. Developed through a collaboration between Dong-A ST and HK inno.N, SC3499 recruits the cereblon (CRBN) E3 ubiquitin ligase to induce the proteasomal degradation of mutant EGFR. This mechanism allows the compound to overcome resistance to third-generation EGFR tyrosine kinase inhibitors (TKIs) like osimertinib, including resistance mediated by secondary mutations such as C797S and T790M. Preclinical data presented at AACR 2026 demonstrated that SC3499 provides potent and durable antitumor activity in L858R-driven non-small cell lung cancer (NSCLC) models while sparing wild-type EGFR and other CRBN substrates.