Chemicals & Small Molecules

Geranyl thiolodiphosphate (GSPP) is an analog of GPP in which the non-bridging oxygen has been replaced by sulfur resulting in a less-reactive compound. GSPP is turned over by avian farnesyl diphosphate synthase (FPPase) more slowly than FPP and acts as a competitive inhibitor (KI = 24.8 μM). Powered by Bioz See more details on Bioz

Farnesyl thiolodiphosphate (FSPP) is an analog of FPP in which the non-bridging oxygen has been replaced by sulfur resulting in a less-reactive compound. Powered by Bioz See more details on Bioz

Echelon's fluorogenic Autotaxin (ATX) substrate FS-3 (L-2000) is a doubly labeled analog of LPC wherin the fluorophore is quenched through intramolecular energy transfer. Hydrolysis of the substrate produces an increase in fluorescence.Autotaxin which has lysophospholipase D (lysoPLD) activity cleaves choline from lysophosphatidylcholine forming lysophosphatidic acid (LPA) a potent mitogen that as been implicated in the pathophysiology of ovarian cancer. LysoPLD/ATX has been demonstrated to increase cell motility neovascularization proliferation and aggressiveness of tumors and is upregulated in numerous cancer lineages (non-small cell lung glioma mammary carcinoma renal cell carcinoma hepatocellular carcinoma). In addition dysregulation of the ATX/LPA pathway is central to the pathophysiology of idiopathic pulmonary fibrosis rheumatoid arthritis and other inflammatory diseases. Modulation of ATX activity through small-molecules is a target with high potential for novel ca

ATX-Red AR-2 is an in vivo imaging probe for visualizing and measuring ATX activity. It is an analog of the autotaxin substrate lysophosphatidylcholine (LPC) and contains a near-infrared fluor (Licor IRDye® 800CW) and quencher (Licor IRDye® QC-1). The design is modeled after FS-3 a fluorogenic ATX substrate that is predictive of ATX activity. In the parent compound fluorescence is quenched through intramolecular energy transfer but when autotaxin cleaves ATX-Red AR-2 fluorescence increases. This activation mechanism is specific to autotaxin in vitro and in vivo.Autotaxin which has lysophospholipase D (lysoPLD) activity cleaves choline from lysophosphatidylcholine forming lysophosphatidic acid (LPA) a potent mitogen that as been implicated in the pathophysiology of ovarian cancer. LysoPLD/ATX has been demonstrated to increase cell motility neovascularization proliferation and aggressiveness of tumors and is upregulated in numerous cancer lineages (non-small cell lung glioma

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.