Protease inhibitors, compositions and methods of use
This invention relates to grassystatins A, B and C, and their isolated or purified forms. The compounds of the invention are useful as aspartic protease, gamma secretase, or metalloprotease inhibitors. Methods of using the compounds and compositions thereof are also disclosed.
1. An isolated compound selected from the group of grassystatins A, B and C as follows:
or a pharmaceutically acceptable salt, ester, amide, hydrate, stereoisomer, or solvate thereof.
2. A pharmaceutical composition comprising a compound selected from the group of grassystatins A, B and C, or a pharmaceutically acceptable salt, ester, amide, hydrate, stereoisomer, or solvate thereof, together with a pharmaceutically acceptable carrier or diluent.
3. A method of treating a disease or disorder in a subject, the method comprising administering to the subject an effective amount of a compound selected from the group of grassystatins A, B and C, or a pharmaceutically acceptable salt, ester, hydrate, or solvate thereof, wherein the disease or disorder is selected from the group consisting of disorders of the cell cycle, neurodegenerative disorders, cancer, and Alzheimer's disease.
4. A method of inhibiting T-cell proliferation in a subject, the method comprising administering to the subject an effective amount of a compound selected from the group of grassystatins A and B, or a pharmaceutically acceptable salt, ester, hydrate, or solvate thereof.
5. The method of claim 4 , comprising reducing IL-17 production in a subject or in a cell, the method comprising administering to the subject or the cell an effective amount of a compound selected from the group of grassystatins A and B, or a pharmaceutically acceptable salt, ester, hydrate, or solvate thereof.
6. The method of claim 4 , comprising reducing IFN-γ production in a subject or in a cell, the method comprising administering to the subject or the cell an effective amount of a compound selected from the group of grassystatins A and B, or a pharmaceutically acceptable salt, ester, hydrate, or solvate thereof.
7. A method of treating a disease or disorder in a subject, the method comprising administering to the subject an effective amount of a compound selected from the group of grassystatins A and B, or a pharmaceutically acceptable salt, ester, hydrate, or solvate thereof, wherein the disease or disorder is selected from the group consisting of infection, autoimmune disorders, allergic diseases, and transplant rejection.