ULK1 Activator

UE01 is an orally available, selective small-molecule modulator targeting both ULK1/ERK1/2. UE01 activates human ULK1 with an EC₅₀ of 695.30 nM and a K_D of 114.3 nM for ULK1. It inhibits ERK1 with an IC₅₀ of 179.90 nM and a K_D of 114 nM for ERK1, while showing weak binding to ERK2 with a K_D of 2.8 mM. UE01 induces the conformational transition of ULK1 from an inactive to an active state, enhances the phosphorylation of ULK1 Ser317 and mAtg13 Ser355, and reduces the phosphorylation of ULK1 Ser757. UE01 also competitively occupies the ATP-binding pocket of ERK1, inhibits ERK1 kinase activity, and decreases the activity of the ERK1/2 signaling pathway. UE01 induces complete autophagy flux and apoptosis, upregulates Atg5, Atg7, LC3-II/LC3-I, Bax, cytochrome C (Cyt c), Cleaved-Caspase 3, Cleaved-PARP1 and E-cadherin, downregulates p62, Bcl-2, MMP-2 and MMP-9, reduces the phosphorylation of Exo70 Ser250, and promotes the proteasome-dependent degradation of Cav-1, thereby inhibiting EMT-related phenotypes and extracellular matrix degradation. UE01 inhibits the proliferation, colony formation, 3D tumor sphere growth, DNA synthesis, migration and invasion of triple-negative breast cancer cells, and can be used in studies related to triple-negative breast cancer.

BL-918 is an orally active UNC-51-like kinase 1 (ULK1) activator with an EC₅₀ of 24.14 nM. BL-918 exerts its cytoprotective autophagic effect by targeting ULK complex. BL-918 has the potential for Parkinson’s disease (PD) treatment.

LYN-1604 dihydrochloride is a potent UNC-51-like kinase 1 (ULK1) activator (EC₅₀=18.94 nM) for the research of triple negative breast cancer (TNBC).

LYN-1604 is a potent UNC-51-like kinase 1 (ULK1) activator (EC₅₀=18.94 nM) for the research of triple negative breast cancer (TNBC).

LYN-1604 hydrochloride is a potent UNC-51-like kinase 1 (ULK1) activator (EC₅₀=18.94 nM) for the research of triple negative breast cancer (TNBC).