VU0359595 (ML-270) is a potent and selective pharmacological phospholipase D1 (PLD1) inhibitor with an IC50 of 3.7 nM. VU0359595 is >1700-fold selective for PLD1 over PLD2 (IC50 of 6.4 μM). VU0359595 can be used for the research of cancer, diabetes, neurodegenerative and inflammatory diseases.

PLD2:6.4 μM, PLD1:3.7 nM

VU0359595, at concentrations ranging from 5 to 5000 nM, inhibits both the baseline and FCS/IGF-1 stimulated proliferation of astroglial cells. At doses of 5, 50, and 500 nM, with a 30-min exposure, it does not impact the basal phospholipase D (PLD) activity in astrocytes; however, it significantly reduces mitogen-stimulated PLD activity in a concentration-dependent manner[2]. Additionally, at a concentration of 0.15 μM administered 1 h before and during a 4 h high glucose treatment, VU0359595 notably decreases the high glucose-induced increase in [3H]-phosphatidylethanol (PEth) generation in retinal pigment epithelium (RPE) cells[3]. When applied at 5 μM one hour before lipopolysaccharide (LPS) treatment, it modulates autophagy in LPS-induced RPE cells undergoing a 24-h treatment with 10 μg/ml of LPS[4]. Furthermore, a 2 nM pre-exposure for 30 min effectively blocks the gliotoxin (50 ng/ml)-enhanced internalization of A. fumigatus in A549 cells[5].