Table 2. Targeting autophagy through the phosphoinositide network.

The role of phosphoinositides in human diseases is intimately linked to the key roles they hold in autophagy. Efforts to identify specific molecules have demonstrated that targeting autophagy through the kinases and phosphatases that regulate phosphoinositides is a valid therapeutic strategy of relevance for many human diseases. This table includes some of the most promising molecules that modulate autophagy parallel to a reduction in disease-related phenotypes.

Target	Molecule	Disease relevance	Autophagy phenotype	In vivo validation	Reference
Phosphatase inhibitors
MTMR14	Auten 67	Aging, neuroprotection	Increased autophagy flux	Mouse model for Alzheimer’s	Papp et al. 2016
MTMR14	Auten 99	Aging, neuroprotection	Increased autophagy flux	Drosophila models for Parkinson’s and Huntington’s	Kovács et al. 2017
OCRL INPP5B	YU142670	Lowe syndrome	Accumulation of autophagosomes, decreased autophagy flux	PTCs derived from patients	Pirruccello et al. 2014 De Leo et al. 2016
Kinase inhibitors
PIK3C3	SAR405	Cancer	Late endosome defects, blocks autophagy	Renal tumor cells	Ronan et al. 2014
PIK3C3	PIK-III	N/A	Inhibits autophagy; stabilization of autophagy substrates;	N/A	Dowdle et al. 2014
PIKfyve	Apilimod	Cancer/Non-Hodgkin lymphoma	Inhibits TFEB, lysosomal genes	Mouse xenografts	Gayle et al. 2017
PIKfyve	WX8-family	Cancer/melanoma	Inhibit lysosome fission, traffic into the lysosome, autophagosome formation	Tumor derived cell lines	Sharma et al. 2019
PI5P4Kγ	NCT-504	Huntington’s disease	Increased autophagic flux	Rat primary cortical neurons, Drosophila HD model	Al-Ramahi et al. 2017
PI5P4K	I-OME Tryphostin AG-538	Cancer	Predicted	N/A	Davis et al. 2013
PI5P4K	SAR088	Diabetes	Predicted	Obese SDF mice	Voss et al. 2014