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Chemical Compound Review:

CHEMBL146186 3-[3-(aminocarbonylmethyl)-1- benzyl-2...

Synonyms: SureCN7965980, CTK8E7560, LY-311727, AC1L4F87, LY311727, ...

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Disease relevance of AIDS-122625

IT LY311727 also suppressed thermal hyperalgesia induced by IT injection of substance P (30 nmol) [1].

High impact information on AIDS-122625

Furthermore, the optimized structure (LY311727) displayed 1,500-fold selectivity when assayed against porcine pancreatic s-PLA2 [2].
Interestingly, the expression of sPLA2-IIA induced by TNF alpha alone is also attenuated by MK886, by the sPLA2-IIA inhibitor LY311727, by heparinase, which prevents the binding of sPLA2-IIA to heparan sulfate proteoglycans, and by the specific cPLA2-alpha inhibitor pyrrolidine-1 [3].
TNF-induced NF-kappaB activation was also strongly reduced in cells stimulated in the presence of the secretory PLA2 (sPLA2) inhibitors 12-epi-scalaradial and LY311727 [4].
However, the sPLA(2) activity observed in spinal cord homogenates was suppressed by addition of LY311727, a selective sPLA(2) inhibitor [1].
This was supported by the finding that the LPS-induced chemokine production was not affected by the selective sPLA(2) inhibitor LY311727 [5].

Gene context of AIDS-122625

Treatment with IFN-gamma and IL-1alpha for 15 min induced a rapid increase of AA release from NHBE cells, which was blocked by the cPLA(2) inhibitor MAFP (p<0.05) but not by the sPLA(2) inhibitor LY311727 or iPLA(2) inhibitor HELSS [6].

References

Spinal phospholipase A2 in inflammatory hyperalgesia: role of the small, secretory phospholipase A2. Svensson, C.I., Lucas, K.K., Hua, X.Y., Powell, H.C., Dennis, E.A., Yaksh, T.L. Neuroscience (2005) [Pubmed]
Structure-based design of the first potent and selective inhibitor of human non-pancreatic secretory phospholipase A2. Schevitz, R.W., Bach, N.J., Carlson, D.G., Chirgadze, N.Y., Clawson, D.K., Dillard, R.D., Draheim, S.E., Hartley, L.W., Jones, N.D., Mihelich, E.D. Nat. Struct. Biol. (1995) [Pubmed]
Potentiation of tumor necrosis factor alpha-induced secreted phospholipase A2 (sPLA2)-IIA expression in mesangial cells by an autocrine loop involving sPLA2 and peroxisome proliferator-activated receptor alpha activation. Beck, S., Lambeau, G., Scholz-Pedretti, K., Gelb, M.H., Janssen, M.J., Edwards, S.H., Wilton, D.C., Pfeilschifter, J., Kaszkin, M. J. Biol. Chem. (2003) [Pubmed]
Selective inhibitors of cytosolic or secretory phospholipase A2 block TNF-induced activation of transcription factor nuclear factor-kappa B and expression of ICAM-1. Thommesen, L., Sjursen, W., Gåsvik, K., Hanssen, W., Brekke, O.L., Skattebøl, L., Holmeide, A.K., Espevik, T., Johansen, B., Laegreid, A. J. Immunol. (1998) [Pubmed]
Inhibition of LPS-induced chemokine production in human lung endothelial cells by lipid conjugates anchored to the membrane. Beck, G.C.h., Yard, B.A., Schulte, J., Oberacker, R., van Ackern, K., van Der Woude, F.J., Krimsky, M., Kaszkin, M., Yedgar, S. Br. J. Pharmacol. (2002) [Pubmed]
Involvement of p38 and p42/44 MAP kinases and protein kinase C in the interferon-gamma and interleukin-1alpha-induced phosphorylation of 85-kDa cytosolic phospholipase A(2) in primary human bronchial epithelial cells. Wu, T., Han, C., Shelhamer, J.H. Cytokine (2004) [Pubmed]

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