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UNC-51-like Kinase 1: From an Autophagic Initiator to Multifunctional Drug Target.
Journal of Medicinal Chemistry 2018 August 10
UNC-51-like kinase 1 (ULK1), known as an ortholog of the yeast Atg1, is the serine-threonine kinase and the autophagic initiator in mammals. Accumulating evidence has recently revealed the kinase domain structure of ULK1 and its post-translational modifications, as well as further elucidated its regulatory autophagic pathways and associations with diverse human diseases. Interestingly, a series of small molecules have been recently reported to target ULK1 or ULK1-modulating autophagy, which may provide a clue on exploiting them as novel candidate drugs. Taken together, this review discusses how ULK1 acts as an autophagic initiator for modulation of its intricate mechanisms, as well as how ULK1 becomes a multifunctional target for potential therapeutic applications.
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