LYN-1604

LYN-1604 (CAS No.: 2088939-99-3) is a synthetic small-molecule research probe used as a selective ULK1 activator for mechanistic studies in autophagy biology, apoptosis crosstalk, and oncology-related models (especially triple-negative breast cancer, TNBC); its target, ULK1, is a serine/threonine kinase responsible for key regulation of autophagy initiation. In cell-level studies, LYN-1604 can upregulate Beclin 1, LC3?II, and total LC3 and reduce p62 in a concentration-dependent manner in TNBC models such as MDA-MB-231, showing molecular features of enhanced autophagic flux, while promoting caspase?3 cleavage and inducing a cell-death phenotype; the related effects are associated with the involvement of the ATF3 and RAD21 pathways. The functional activation potency of this compound toward ULK1 is in the tens of nanomolar range, its potency in inhibiting TNBC cell viability is in the low micromolar range, and this cell-viability effect can be partially reversed by the autophagy inhibitor 3?methyladenine, indicating a ULK1-dependent mode of action. Biochemical and biophysical evidence shows that LYN-1604 can directly bind wild-type ULK1 with submicromolar affinity, while its affinity for the Y89A variant is significantly reduced compared with wild-type and variants such as K50A and L53A, supporting its specific binding at functionally relevant residue sites. Typical applications include ULK1 target validation, analysis of autophagy and apoptosis pathways centered on LC3 conversion and p62 turnover, cell viability and cell-death phenotype assays, chemical biology studies combined with genetic or pharmacological interventions, and exploratory studies in oncology-related cellular and mouse xenograft models; under controlled conditions in in vivo MDA-MB-231 xenograft experiments, tumor growth inhibition signals can be observed, for elucidating ULK1-driven in situ signaling events without involving any clinical use. The specific concentration or dose used in experiments usually depends on the research objective and experimental design, and the overall in vitro activity can be summarized as ranging from nanomolar to low micromolar. For research use only, not for human or veterinary use.