A ULK1 activator
LYN-1604 is an activator of unc-51-like kinase 1 (ULK1; EC50 = 18.94 nM).1 It increases Beclin 1, LC3-II, and total LC3 protein levels and reduces levels of p62 in human MDA-MB-231 triple-negative breast cancer (TNBC) cells in a concentration-dependent manner, indicating an increase in autophagy. It also increases the cleavage of the pro-apoptotic protein caspase-3. LYN-1604 decreases the viability of MDA-MB-231 cells in vitro (IC50 = 1.66 μM), an effect that can be reversed by the autophagy inhibitor 3-methyladenine . LYN-1604 (25, 50, and 100 mg/kg) reduces tumor growth in an MDA-MB-231 mouse xenograft model.
1.Zhang, L., Fu, L., Zhang, S., et al.Discovery of a small molecule targeting ULK1-modulated cell death of triple negative breast cancer in vitro and in vivoChem. Sci.8(4)2687-2701(2017)
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