Compositions and methods for treatment
The present invention provides compounds and methods for the treatment of LFA-1 mediated diseases. In particular, LFA-1 antagonists are described herein and these antagonists are used in the treatment of LFA-1 mediated diseases. One aspect of the invention provides for diagnosis of an LFA-1 mediated disease and administration of a LFA-1 antagonist, after the patient is diagnosed with a LFA-1 mediated disease. In some embodiments, the LFA-1 mediated diseases treated are dry eye disorders. Also provided herein are methods for identifying compounds which are LFA-1 antagonists.
1 . A method of identifying LFA-1 antagonists, said compounds being competitive inhibitors of the LFA-1: ICAM interaction, comprising:
binding an antagonist candidate molecule at a known concentration to a ligand selected from group comprising ICAM-1, s-ICAM-1, and LFA-1 in a binding assay;
adding a set of concentrations of a labeled compound, wherein said compound is known to be an inhibitor of a LFA-1 and ICAM interaction on the I domain of the alpha chain of LFA-1;
obtaining a binding curve;
determining EC50 values for each set of binding competitions; and
determining the antagonistic properties of said candidate molecule based on said EC50 values.
2 . The method of claim 1 wherein said labeled compound comprises a compound of Formula VII: