Assay for identification therapeutic agents
AssigneeFred Hutchinson Cancer Research Center
InventorsJames A. Bianco, Stuart L. Bursten, Jack W. Singer
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Abstract
There is disclosed a method for screening for inhibitors of cellular second messenger signaling regulated by lysophosphatidic acid acyl transferase (LPAAT) and phosphatidic acid phosphohydrolase (PAPH), which method comprises contacting target cells or appropriate subcullular elements under appropriate conditions of stimulation with a candidate drug and assessing the levels of the relevant subsets of phosphatidic acid (PA) and diacylglycerol (DAG) in the presence and absence of the candidate drug.
Claims4
An assay for selecting a therapeutic agent which lowers cellular levels of unsaturated, non-arachidonate phosphatidic acid (PA) and diacylglycerol (DAG) in target cells, comprising:
- contacting a first sample of target cells containing PA and DAG with a stimulus which induces increased levels of PA and DAG in the target cell, wherein the target cell is mammalian and derived from mesenchymal, neutrophil or ectodermal embryonic origins or is a transformed cell containing an activated oncogene, a marrow stromal cell or a synaptosome derived from brain cells, or is a subcellular fraction thereof;
- determining levels of PA and DAG in said target cells at various time intervals after contacting with the stimulus;
- contacting a second sample of said target cells with said stimulus in the presence of a candidate therapeutic agent;
- determining levels of said PA and DAG in said second sample of target cells at various time intervals after said contacting;
- and
- correlating the levels of said PA and DAG determined in the presence and absence of said candidate therapeutic agent to select the therapeutic agent which lowers cellular levels of said PA or DAG.
Dependencies are inferred from the claim text.