VU0359595

Names

[ Name ]:
VU0359595

[Synonym ]:
Cyclopropanecarboxamide, N-[(1S)-2-[4-(5-bromo-2,3-dihydro-2-oxo-1H-benzimidazol-1-yl)-1-piperidinyl]-1-methylethyl]-2-phenyl-, (1R,2R)-
(1R,2R)-N-{(2S)-1-[4-(5-Bromo-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)-1-piperidinyl]-2-propanyl}-2-phenylcyclopropanecarboxamide

Biological Activity

[Description]:

VU0359595 (CID-53361951; 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[1][2][3][4].

[Related Catalog]:

Research Areas >> Cancer

Research Areas >> Infection

Signaling Pathways >> Metabolic Enzyme/Protease >> Phospholipase

Research Areas >> Inflammation/Immunology

Research Areas >> Metabolic Disease

Research Areas >> Neurological Disease

[Target]

PLD1:3.7 nM (IC50)

PLD2:6.4 μM (IC50)

[In Vitro]

VU0359595 (5, 50, 500, 5000 nM) inhibits basal and FCS/IGF-1 stimulated proliferation of astroglial cells[2] . VU0359595 (5, 50, 500 nM; 30 min) does not affect basal PLD activity in astrocytes but reduces mitogen-stimulated PLD activity in a concentration-dependent manner[2]. VU0359595 (0.15 μM; 1 h before high glucose treatment and 4 h during high glucose treatment) partially reduces the increase [3H]-phosphatidylethanol (PEth) generation induced by high glucose (33 mM) in retinal pigment epithelium (RPE) cells[3]. VU0359595 (5 μM; 1 h prior to LPS treatment) modulates the autophagic process of LPS-induced (10 μg/ml; 24 h) RPE cells[4].

[References]

[1]. Lewis JA, et al. Design and synthesis of isoform-selective phospholipase D (PLD) inhibitors. Part I: Impact of alternative halogenated privileged structures for PLD1 specificity. Bioorg Med Chem Lett. 2009;19(7):1916-1920.

[2]. Burkhardt U, et al. Phospholipase D is a target for inhibition of astroglial proliferation by ethanol. Neuropharmacology. 2014;79:1-9.

[3]. Tenconi PE, et al. High glucose-induced phospholipase D activity in retinal pigment epithelium cells: New insights into the molecular mechanisms of diabetic retinopathy. Exp Eye Res. 2019;184:243-257.

[4]. Bermúdez V, et al. Lipopolysaccharide-Induced Autophagy Mediates Retinal Pigment Epithelium Cells Survival. Modulation by the Phospholipase D Pathway. Front Cell Neurosci. 2019;13:154. Published 2019 Apr 24.

Chemical & Physical Properties

[ Density]:
1.4±0.1 g/cm3

[ Molecular Formula ]:
C₂₅H₂₉BrN₄O₂

[ Molecular Weight ]:
497.427

[ Exact Mass ]:
496.147369

[ LogP ]:
4.71

[ Index of Refraction ]:
1.631

Safety Information

[ RIDADR ]:
NONH for all modes of transport

Articles

β-1,3-Glucan-induced host phospholipase D activation is involved in Aspergillus fumigatus internalization into type II human pneumocyte A549 cells.

PLoS ONE 6 , e21468, (2011)

The internalization of Aspergillus fumigatus into lung epithelial cells is a process that depends on host cell actin dynamics. The host membrane phosphatidylcholine cleavage driven by phospholipase D ...