Atg4D Inhibitors

Atg4D Inhibitors consist of a diverse group of chemical compounds that interfere with the autophagic flux, thereby indirectly inhibiting the proteolytic activity of Atg4D on LC3-related proteins, which is essential for the autophagic process. For example, inhibitors of vacuolar H+-ATPase, such as Concanamycin A and Bafilomycin A1, prevent the acidification of lysosomes, a necessary step for the fusion of autophagosomes with lysosomes. Without proper acidification, the degradation of autophagic substrates is impaired, which in turn can affect the activity of Atg4D. Atg4D is crucial for preparing LC3-related proteins through delipidation, a process that allows the recycling of these proteins and the promotion of further autophagic events.

Other compounds, like Chloroquine and 3-Methyladenine, inhibit autophagy by different mechanisms. Chloroquine increases the pH of intracellular vesicles, which disrupts autophagosome maturation, while 3-Methyladenine inhibits class III PI3K, preventing the formation of autophagosomes at an early stage.