Modulators of angiogenesis and tumorigenesis
AssigneeRigel Pharmaceuticals, Inc.
InventorsJames B. Lorens, Robert E. Atchison, Annabelle Friera, Sacha Holland
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Abstract
The present invention relates to regulation of angiogenesis and tumorigenesis. The invention further relates to methods for identifying and using agents, including small organic molecules, antibodies, peptides, cyclic peptides, nucleic acids, antisense nucleic acids, RNAi, and ribozymes, that modulate angiogenesis via modulation of endothelial cell haptotaxis; as well as to the use of expression profiles and compositions in diagnosis and therapy of angiogenesis and cancer.
Claims13
A method for identifying a compound that inhibits angiogenesis, the method comprising:
- assaying in vitro kinase activity of an Axl polypeptide comprising an amino acid sequence with greater than about 95% identity to full length SEQ ID NO:
- 4 in the presence of the compound, wherein the Axl polypeptide has kinase activity in the absence of said compound;
- performing a cell-based assay in an endothelial cell comprising said Axl polypeptide in the presence of the compound, which assay produces an angiogenesis phenotype selected from the group consisting of αvβ3 expression, tube formation, and haptotaxis in said endothelial cell in the absence of the compound;
- and
- identifying a compound that inhibits the in vitro kinase activity of the Axl polypeptide and that inhibits the angiogenesis phenotype in the cell-based assay,
- wherein inhibition of the in vitro kinase activity of the Axl polypeptide in the presence of the compound and inhibition of the angiogenesis phenotype in the cell-based assay in the presence of the compound identifies the compound as a compound that inhibits angiogenesis.
An in vitro method for identifying a compound that inhibits angiogenesis, the method comprising:
- contacting the compound with an endothelial cell that expresses a recombinant Axl polypeptide comprising an amino acid sequence with greater than about 95% identity to full length SEQ ID NO:
- 4, wherein the Axl polypeptide has kinase activity in the absence of said compound;
- performing a cell-based assay, which assay produces an angiogenesis phenotype selected from the group consisting of αvβ3 expression, tube formation, and haptotaxis in said endothelial cell in the absence of the compound;
- and
- identifying a compound that inhibits the angiogenesis phenotype in the cell-based assay,
- wherein inhibition of the angiogenesis phenotype in the cell-based assay in the presence of the compound identifies the compound as a compound that inhibits angiogenesis.
Dependencies are inferred from the claim text.