HEPTbeta AS A TARGET IN TREATMENT OF ANGIOGENISIS MEDIATED DISORDERS

Abstract

Disclosed herein is the use of HPTPbeta to screen agents useful in the treatment angiogenesis mediated disorders.

1 . A pharmaceutical composition, comprising:
 a) an effective amount of a modulator of Human Protein Tyrosine Phosphatase beta (HPTPbeta) activity wherein the effective amount is determined by exposing a compound to HPTPbeta and determining the amount by which the agent modulates HPTPbeta activity; and   b) a pharmaceutically-acceptable carrier.   
     
     
         2 . A composition according to  claim 1 , wherein the modulator of HPTPbeta activity is an HPTPbeta inhibitor. 
     
     
         3 . A pharmaceutical composition for modulating an angiogenesis mediated disorder, comprising:
 a) an HPTPbeta inhibitor which is determined as useful for treating an angiogenesis mediate disorder by a method comprising:
 i) exposing an agent to Human Protein Tyrosine Phosphatase-beta (HPTPbeta) and Vascular Endothelial Growth Factor Receptor-type 2 (VEGFR2); and 
 ii) identifying whether the agent modulates HPTPbeta activity and VEGFR2 activity; and 
   b) a pharmaceutically-acceptable carrier;   wherein the inhibitor is not heparin.   
     
     
         4 . The composition according to  claim 3 , wherein the angiogenesis mediated disorder is selected from:
 i) disorders, diseases, and/or unwanted conditions characterized by unwanted or elevated angiogenesis selected from the group consisting or diabetic retinopathy, macular degeneration, sickle cell anemia, syphilis, pseudoxanthoma elasticum, Paget's disease, vein or artery occlusion, carotid obstructive disease, chronic uveitus, chronic vitritis, mycobacterial infections, Lyme's disease, systemic lupus, erythematosis, retinopathy of prematurity, Eales' disease, Behcet's disease, presumed ocular histoplasmosis, Best's disease, optic pits, Stargardt's disease, pars planitis, chronic retinal detachment, hyperviscosity syndromes, toxoplasmosis, proliferative vitroeretinopathy, Crohn's disease, ulcerative colitis, psoriasis, sarcoidosis, rheumatoid arthritis, hemangiomas, Osler-Weber-Rendu disease, hereditary hemorrahic telangiectasia, solid tumors, blood borne tumors, and acquired immune deficiency syndrome; or   ii) disorders, diseases, and/or unwanted conditions characterized by wanted or reduced angiogenesis selected from the group consisting of skeletal muscle ischemia, myocardial ischemia, stroke, coronary artery disease, peripheral vascular disease, and tissue repair where tissue has been damaged by trauma, surgical procedures, irradiation, laceration, toxic chemicals, viral infection, bacterial infection, non-healing wounds, or burns, or where tissue has been damaged by arthritis or osteoporosis.   
     
     
         5 . The composition according to  claim 3  wherein the HPTPbeta inhibitor increases endothelial cell survival when cell survival is measured in an in vitro test wherein the cells are stimulated with 500 μM VEGF 165  or 250 ng/mL of Angiopoietin-1 when compared to untreated cells. 
     
     
         6 . The composition according to  claim 3 , wherein the HPTPbeta inhibitor enhances ligand-induced phosphorylation of VEGFR2 when endothelial cells are pretreated for 30 minutes with 0.1 mM of the inhibitor. 
     
     
         7 . The composition according to  claim 3 , wherein the HPTPbeta inhibitor enhances ligand-induced phosphorylation of VEGFR2 when endothelial cells are pretreated for 30 minutes with 1 mM of the inhibitor. 
     
     
         8 . The composition according to  claim 3 , wherein the HPTPbeta inhibitor enhances ligand-induced phosphorylation of Tie-2 when endothelial cells are pretreated for 30 minutes with 0.1 mM of the inhibitor. 
     
     
         9 . The composition according to  claim 3 , wherein the HPTPbeta inhibitor enhances ligand-induced phosphorylation of Tie-2 when endothelial cells are pretreated for 30 minutes with 1 mM of the inhibitor.