(1R,2R)-N-([S]-1-{4-[5-broMo-2-oxo-2,3-dihydro-1H-benzo(d)iMidazol-1-yl]piperidin-1-yl}propan-2-yl)-2-phenylcyclopropanecarboxaMide Chemical Properties

Density 

1.395±0.06 g/cm3(Predicted)

storage temp. 

2-8°C

solubility 

DMSO: soluble5mg/mL, clear

pka

11.11±0.30(Predicted)

form 

powder

color 

white to beige

Safety Information

WGK Germany 

3

(1R,2R)-N-([S]-1-{4-[5-broMo-2-oxo-2,3-dihydro-1H-benzo(d)iMidazol-1-yl]piperidin-1-yl}propan-2-yl)-2-phenylcyclopropanecarboxaMide Usage And Synthesis

Uses

VU0359595 is an inhibitor of phospholipase D1 (PLD1) which is more than 1700 fold selective over phospholipase D2 (PLD2). This complex only binds and inhibit phospholipase D though an allosteric site, but it noes not interact with the catalytic site of phospholipase D.

Biological Activity

vu0359595 is a potent and selective inhibitor of pld1.phospholipase d (pld) isozymes mediate phospholipid hydrolysis and transphosphatidylation. until now, two mammalian isoforms of pld, pld1, and pld2, have been identified. it has been identified that pld has been implicated in a human cancer cell progression, actin cytoskeleton reorganization and cell motility [1].

in vitro

vu0359595 was an inhibitor of pld1 with an ic50 of 3.7 nm. vu0359595 showed >1,700-fold selectivity over pld2. the ic50 of was vu0359595 against pld2 was 6.4 μm [1]. preliminary evidence has demonstrated that vu0359595 showed no interaction with the catalytic site of pld, but may bind and inhibit pld through an allosteric site [1]. at 500 nm, vu0359595 significantly reduced the pld activity in astroglial cultures from wild-type mice by 58% [2]. in cells stimulated by 1% fcs, vu0359595 decreased cell proliferation in wild-type and pld2-deficient cells at a concentration of 500 nm [2]. vu0359595 (500 nm) significantly reduced cell growth in cells stimulated by either mitogen [2].

References

[1] lewis j a, scott s a, lavieri r, et al. design and synthesis of isoform-selective phospholipase d (pld) inhibitors. part i: impact of alternative halogenated privileged structures for pld1 specificity[j]. bioorganic & medicinal chemistry letters, 2009, 19(7): 1916-1920.
[2] burkhardt u, beyer s, klein j. role of phospholipases d1 and 2 in astroglial proliferation: effects of specific inhibitors and genetic deletion[j]. european journal of pharmacology, 2015, 761: 398-404.

(1R,2R)-N-([S]-1-{4-[5-broMo-2-oxo-2,3-dihydro-1H-benzo(d)iMidazol-1-yl]piperidin-1-yl}propan-2-yl)-2-phenylcyclopropanecarboxaMide(1246303-14-9)Related Product Information

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