Serine/threonine-protein kinase ULK1 (ULK1)

Serine/threonine-protein kinase ULK1 is a key enzyme that initiates autophagy, a process essential for degrading damaged organelles and proteins within cells. It forms part of the core mammalian ULK complex—alongside FIP200/RB1CC1, ATG13, and ATG101—which responds primarily to nutrient deprivation by integrating upstream signals from mTORC1 (inhibitory) and AMPK (activating). Upon activation during cellular stress such as starvation or oxidative damage, ULK1 phosphorylates multiple downstream effectors including Beclin 1/VPS34 complex components—triggering phagophore formation that leads ultimately to mature autophagosomes. Dysregulation of this pathway has been implicated in cancer progression/resistance mechanisms as well as neurodegenerative disorders; thus it is an emerging therapeutic target especially within oncology pipelines where small-molecule inhibitors are being developed.

Other names

Unc-51-like kinase 1Unc-51 like autophagy activating kinase 1Autophagy-related protein 1 homologATG1 (homologous to yeast Atg1)hATG1

Drugs targeting ULK1 generally act as ULK1 inhibitors, blocking its serine/threonine kinase activity. This inhibition disrupts the initiation of autophagy, which can sensitize cancer cells to stress or cytotoxic agents by preventing their survival mechanism under nutrient deprivation or other stresses.