LYN-1604

LYN-1604 is a first-in-class small molecule activator of Unc-51-like kinase 1 (ULK1), a critical initiator of the macroautophagy pathway. Discovered through a combination of in silico screening and chemical synthesis, LYN-1604 binds to the ULK1 kinase domain, specifically interacting with residues Lys50, Leu53, and Tyr89, to enhance its enzymatic activity. In the context of oncology, particularly triple-negative breast cancer (TNBC) where ULK1 is frequently downregulated, LYN-1604 induces autophagy-associated cell death (ACD) and apoptosis. Beyond its anti-tumor potential in TNBC, pancreatic cancer, and clear cell renal cell carcinoma, LYN-1604 has demonstrated preclinical efficacy in diverse conditions including dry eye disease (by alleviating ocular surface inflammation), ischemic stroke (by promoting anti-inflammatory microglial activation), and neurodevelopmental disorders such as Tuberous Sclerosis Complex (by restoring neuronal network connectivity).

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