Methods of treating intraocular pressure with activators of Tie-2
Disclosed herein are compounds effective for activation of Tie-2 and inhibition of HPTP-beta. The compounds can provide effective therapy for eye conditions associated with angiogenesis, for example, intraocular pressure, ocular hypertension, and glaucoma.
1. A method for treating glaucoma in a subject in need thereof, the method comprising administering to the subject a therapeutically-effective amount of a Tie-2 activator, wherein:
the administration reduces intraocular pressure by about 0.1 mmHg to about 9 mmHg compared to absence of administration;
the subject expresses Ang-1 and Ang-2;
the subject is human; and
the Tie-2 activator is a compound of the formula:
or a pharmaceutically-acceptable salt, tautomer, or zwitterion thereof.
2. The method of claim 1 , wherein the Tie-2 activator binds a phosphatase.
3. The method of claim 1 , wherein the Tie-2 activator inhibits a phosphatase.
4. The method of claim 1 , wherein the Tie-2 activator binds HPTP-B.
5. The method of claim 1 , wherein the Tie-2 activator inhibits HPTP-B.
6. The method of claim 1 , wherein the Tie-2 activator is a phosphate mimetic.
7. The method of claim 1 , wherein the therapeutically-effective amount is from about 1 mg to about 100 mg.
8. The method of claim 7 , wherein the therapeutically-effective amount is from about 0.5 mg to about 30 mg.
9. The method of claim 8 , wherein the therapeutically-effective amount is about 15 mg.
10. The method of claim 8 , wherein the therapeutically-effective amount is about 22.5 mg.
11. The method of claim 1 , wherein the therapeutically-effective amount is about 30 mg.
12. The method of claim 1 , wherein the administration is to an eye of the subject.
13. The method of claim 1 , wherein the administration is intravitreal.
14. The method of claim 1 , wherein the administration is subcutaneous.
15. The method of claim 1 , wherein the administration is topical.
16. The method of claim 1 , wherein the administration is topical to an eye of the subject.
17. The method of claim 1 , wherein the Tie-2 activator, or a pharmaceutically-acceptable salt thereof, is formulated as a drop.
18. The method of claim 1 , wherein the Tie-2 activator, or a pharmaceutically-acceptable salt thereof, is formulated as a drop, wherein the drop is administered to an eye of the subject.
19. The method of claim 1 , wherein the intraocular pressure is reduced by at least about 2 mmHg.
20. The method of claim 1 , wherein the intraocular pressure is ocular hypertension.