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, 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 currently underexplored target, but one with high potential for novel cancer and anti-inflammatory therapeutics.
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