Therapy of autoimmune colitis using a TIP60 inhibitor
This invention is in the fields of immunology and autoimmunity. More particularly it concerns methods of treating patients with compounds which are useful agents for inhibiting the functions of TIP60 in the treatment of an individual suffering, for example, from ulcerative colitis and other irritable bowel diseases.
1. A method of treating a patient having an autoimmune disorder, the method comprising the step of administering to the patient a therapeutically or prophylactically effective amount of a compound having a structure of Formula 1:
wherein Ar 1 and Ar 2 are each independently C 6 —C 10 aryl or C 5 —C 10 heteroaryl;
R 1 and R 3 are each independently at each occurrence alkyl, halo, hydroxyl, cyano, nitro, or alkoxy;
R 2 is H or alkyl; and
m and n are independently 0, 1, or 2.
2. The method of claim 1 , wherein said compound inhibits histone acetyltransferase (HAT) activity or expression.
3. The method of claim 1 , wherein said compound inhibits TIP60 activity or expression.
4. The method of claim 1 , wherein Ar 1 and Ar 2 are each independently C 6 —C 10 aryl.
5. The method of claim 1 , wherein the compound has a structure of Formula II or Formula III:
where m and n are independently 1 or 2.
6. The method of claim 5 , wherein the compound has a structure of Formula IIA, IIIA, IVA, or IVB:
7. The method of claim 1 , wherein R 2 is H.
8. The method of claim 1 , wherein R 3 is independently at each occurrence halo.
9. The method of claim 8 , wherein R 3 is independently at each occurrence chloro or fluoro.
10. The method of claim 8 , wherein R 1 is independently at each occurrence C 1-3 alkyl, halo, or C 1-3 alkoxy.
11. The method of claim 1 , wherein R 1 is independently at each occurrence halo.
12. The method of claim 11 , wherein R 1 is independently at each occurrence chloro or fluoro.
13. The pharmaceutical composition method of claim 11 , wherein R 3 is independently at each occurrence C 1-3 alkyl, halo, or C 1-3 alkoxy.
14. The method of claim 5 , having a structure of Formula B7, B7A, B7B, B7C, or B7G:
15. The method of claim 1 , wherein the compound having a structure of Formula 1 is administered with a pharmaceutically acceptable carrier in a pharmaceutical composition.
16. The method of claim 1 wherein the autoimmune disorder is caused by a lack of functional suppressor T cells.
17. The method of claim 1 wherein the autoimmune disorder is multiple sclerosis, diabetes mellitus, rheumatoid arthritis, lupus, Hashimoto's disease, polymyositis, inflammatory bowel disease, scleroderma, oophoritis, thyroiditis, Grave's disease, dermatomyositis, pemphigus vulgaris, myasthenia gravis, hemolytic anemia, or Sjogren's disease.
18. The method of claim 17 wherein the inflammatory bowel disease is Crohn's disease or colitis.
19. The method of claim 1 wherein the autoimmune disorder causes rejection of transplanted organ.
20. The method of claim 19 wherein the organ being rejected is a kidney, a heart, or a liver.