A new paper has been published from Ian Ganley’s lab. It describes novel inhibitors of ULK1/2, the only protein kinase in the autophagy core machinery. The new ULK1 inhibitors, MRT67307 and MRT68921, were shown to inhibit ULK1 activity in cells. Treatment led to a block in autophagy flux (i.e. degradation through the lysosome) but not of autophagosome formation (LC3 positive). This was attributed to a block in autophagosome maturation as autophagosomes (LC3 positive) seemed to be stalled at an early stage (Atg5 positive, see the adapted figure below).
Access the article here: Pharmacological Inhibition of ULK1 Kinase Blocks Mammalian Target of Rapamycin (mTOR)-dependent Autophagy J Biol Chem. 2015 May 1;290(18):11376-83