Target Validation Information
Target ID T19160
Target Name Phospholipase A2, membrane associated
Target Type
Clinical Trial
Drug Potency against Target DIDODECANOYLPHLOROGLUCINOL Drug Info IC50 = 10 nM [529718]
2-(4-phenoxyphenoxy)ethanamine Drug Info IC50 = 7300 nM [529868]
BOLINAQUINONE Drug Info IC50 = 200 nM [526069]
DYSIDINE Drug Info IC50 = 2000 nM [526069]
YM-26734 Drug Info IC50 = 85 nM [529718]
OCHNAFLAVONE Drug Info IC50 = 3500 nM [528052]
CACOSPONGIONOLIDE Drug Info IC50 = 3000 nM [534672]
MANOALIDE Drug Info IC50 = 3900 nM [534672]
The Effect of Target Knockout, Knockdown or Genetic Variations Phospholipase A2 (PLA2) catalyses the release of arachidonic acid for generation of lipid mediators of inflammation and is crucial in diverse inflammatory processes. The functions of the secretory PLA2 enzymes (sPLA2), n uMbering nine members in h uMans, are poorly understood, though they have been shown to participate in lipid mediator generation and the associated inflammation. To further understand the roles of sPLA2 in disease, we quantified the expression of these enzymes in the synovial fluid in rhe uMatoid arthritis and used gene-deleted mice to examine their contribution in a mouse model of autoimmune erosive inflammatory arthritis. Contrary to expectation, we find that the group V sPLA2 isoform plays a novel anti-inflammatory role that opposes the pro-inflammatory activity of group IIA sPLA2. Mechanistically, group V sPLA2 counter-regulation includes promotion of immune complex clearance by regulating cysteinyl leukotriene synthesis. These observations identify a novel anti-inflammatory function for a PLA2 and identify group V sPLA2 as a potential biotherapeutic for treatment of immune-complex-mediated inflammation. [529718]
References
Ref 529718Bioorg Med Chem Lett. 2008 Oct 15;18(20):5415-9. Epub 2008 Sep 12.Simplified YM-26734 inhibitors of secreted phospholipase A2 group IIA.
Ref 529868J Med Chem. 2008 Dec 25;51(24):7882-8.Discovery of multitarget inhibitors by combining molecular docking with common pharmacophore matching.
Ref 526069J Nat Prod. 2001 May;64(5):612-5.New sesquiterpene derivatives from the sponge Dysidea species with a selective inhibitor profile against human phospholipase A2 and other leukocyte functions.
Ref 526069J Nat Prod. 2001 May;64(5):612-5.New sesquiterpene derivatives from the sponge Dysidea species with a selective inhibitor profile against human phospholipase A2 and other leukocyte functions.
Ref 529718Bioorg Med Chem Lett. 2008 Oct 15;18(20):5415-9. Epub 2008 Sep 12.Simplified YM-26734 inhibitors of secreted phospholipase A2 group IIA.
Ref 528052Bioorg Med Chem Lett. 2006 May 1;16(9):2373-5. Epub 2006 Feb 28.Synthesis of phospholipase A2 inhibitory biflavonoids.
Ref 534672J Nat Prod. 1998 Jul;61(7):931-5.A new cacospongionolide inhibitor of human secretory phospholipase A2 from the Tyrrhenian sponge Fasciospongia cavernosa and absolute configuration of cacospongionolides.
Ref 534672J Nat Prod. 1998 Jul;61(7):931-5.A new cacospongionolide inhibitor of human secretory phospholipase A2 from the Tyrrhenian sponge Fasciospongia cavernosa and absolute configuration of cacospongionolides.

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