Chemicals

The PLA2 substrate DBPC is a sensitive probe for a continuous fluorogenic detection applicable to both in vitro and cell-based in situ screening assays. Phospholipase A2 (PLA2) is the enzyme which cleaves phospholipids to produce lysophospholipids and free fatty acids. The PLA2 family of enzymes is known to be at least 10 distinct members. sPLA2-V and sPLA2-X are selectively expressed in human airway epithelium and sPLA2-X in various immune cells. The basal expression of a third enzyme sPLA2-IIA is low but becomes highly expressed during inflammation and sepsis. This enzyme has become associated with allergic rhinitis rheumatoid arthritis septic shock and ARDS. PLA2-IIA represents a target for the treatment of inflammatory disease. Powered by Bioz See more details on Bioz

L-3223 (GWJ-23 or GWJ-A-23) is a potent inhibitor of the enzyme autotaxin (Ki = 18 nM). It is an analog of the known ATX inhibitor S32826 and has improved aqueous solubility compared with the parent compound. GWJ-A-23 has been shown to reduce lung collagen bronchoalveolar lavage cell counts total protein LPA and TGF-β levels in an idiopathic pulmonary fibrosis mouse model (Ref. 2). Powered by Bioz See more details on Bioz

S32826  [4-(Tetradecanoylamino) benzyl]phosphonic acid disodium salt] is a potent inhibitor of the enzyme autotaxin with an IC50 in the nanomolar range. S32826 is suitable for in vitro studies using purified components or cultured cells. Due to its short circulation half-life S32826 is not recommended for use in animal models.Publications Powered by Bioz See more details on Bioz1) Ferry G. N. Moulharat et al. (2008). "S32826 a nanomolar inhibitor of autotaxin: discovery synthesis and applications as a pharmacological tool." J Pharmacol Exp Ther 327(3): 809-19.2) Conrotto P. U. Andrasson et al. (2011). "Knock-down of SOX11 induces autotaxin-dependent increase in proliferation in vitro and more aggressive tumors in vivo." Molecular Oncology 5(6): 527.3) Li S. C. Xiong et al. (2012). "ATX and LPA receptor 3 are coordinately up-regulated in lipopolysaccharide-stimulated THP-1 cells through PKR and SPK1-mediated pathways." FEBS Letters 586(6): 792.

BrP-LPA aka LPA bromophosphonate acts as both an Autotaxin inhibitor (94% inhibition at 10 μM) and pan LPA receptor antagonist (LPA1: 1.5 μM LPA2: 1.4 μM LPA3: 1.2 μM LPA4: 0.27 μM). BrP-LPA inhibits the invasiveness of NIH3T3 ras ATX cells by 40% and decreases chemotaxis by 23%. BrP-LPA reduces the size of breast (MDA-MB-231) colon (HCT-116) and melanoma (B16F10) tumors in mouse models. It also attenuates collagen-induced arthritis PPARγ is not activated by BrP-LPA.Publications Powered by Bioz See more details on Bioz1) Jiang G. Y. Xu et al. (2007). "Alpha-substituted phosphonate analogues of lysophosphatidic acid (LPA) selectively inhibit production and action of LPA." ChemMedChem 2(5): 679-90.2) Zhang H. X. Xu et al. (2009). "Dual Activity Lysophosphatidic Acid Receptor Pan-Antagonist/Autotaxin Inhibitor Reduces Breast Cancer Cell Migration In vitro and Causes Tumor Regression In vivo." Cancer Res 69: 54413) Schleicher S. M. D. K. Thotala et al. (2011). "Autotax

XY-17 [(3S)-1-fluoro-3-hydroxy-4-butyl-1-phosphonate (FHBP)] is a fluorinated phosphonate analog of lysophosphatidic acid (LPA). XY-17 is not hydrolyzed by lipid phosphate phosphatase (LPP) and acts as an agonist of the LPA3 receptor.

XY-14 is a competitive inhibitor of Lipid Phosphate Phosphatase 1 (LPP1) which is the major enzyme responsible for degrading lysophosphatidic acid (LPA) in platelets. XY-14 (10 μM) inhibits LPP1 in human pulmonary artery endothelial cells preventing the dephosphorylation of sphingosine 1-phosphate (S1P) to sphingosine. XY-14 is also reported to inhibit LPP2 & LPP3 (1).

2R-OMPT is a metabolically-stabilized analog of Lysophosphatidic Acid (LPA) which acts as potent agonist for the LPA3 receptor. Of the two enantiomers (2S)-OMPT is more potent than (2R)-OMPT showing 5-20 fold more activity in calcium release from LPA3-transfected Sf9 and rat hepatoma Rh7777 cells. (2S)-OMPT is also more potent in inducing calcium release IL-6 production and MAPK and Akt phosporylation in OVCAR3 cells. Powered by Bioz See more details on Bioz

OMPT [L-sn-1-O-oleoyl-2-O-methylglyceryl-3-phosphothionate] is a metabolically-stabilized analog of Lysophosphatidic Acid (LPA) which acts as potent agonist for the LPA3 receptor. Of the two enantiomers (2S)-OMPT is more potent than (2R)-OMPT showing 5-20 fold more activity in calcium release from LPA3-transfected Sf9 and rat hepatoma Rh7777 cells. (2S)-OMPT is also more potent in inducing calcium release IL-6 production and MAPK and Akt phosporylation in OVCAR3 cells.

Alkyl-OMPT (D-sn-1-O-oleyl-2-O-methyl-glyceryl-3-phosphothionate) is a potent agonist for the G-protein-coupled LPA 3 receptor. Alkyl OMPT induces cell migration in cancer cells mediated by activation of LPA1. Alkyl OMPT also activated Ca2+ release via LPA2 activation but with reduced potency relative to sn-1-oleoyl LPA. Powered by Bioz See more details on Bioz