Methods for treating retinoid responsive disorders using selective inhibitors of CYP26A and CYP26B

• US 20050187298A1
• Filed: 12/13/2004
• Published: 08/25/2005
• Est. Priority Date: 12/17/2003
• Status: Active Grant

• Current Assignee: Allergan, Inc. (Canada) (Abbvie Incorporated)
• Original Assignee: Allergan, Inc. (Canada) (Abbvie Incorporated)
• Inventors: Wang, Liming, Li, Ling, Vu, Thong, Yang, Rong, Bhat, Smita, Liu, Xiaoxia, Takeuchi, Janet, Chandraratna, Roshantha A., Beard, Richard, Tsang, Kwok-Yin, Vasudevan, Jayasree
• Granted Patent: US 7,468,391 B2
• Time in Patent Office: Days
• US Class Current: 514/569
• CPC Class Codes: A61K 31/19 Carboxylic acids, e.g. valproic acid salicylic acid A61K31/60
• CPC Class Codes: A61K 31/192 having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid cannabinoids A61K31/658
• CPC Class Codes: A61K 31/35 having six-membered rings with one oxygen as the only ring hetero atom
• CPC Class Codes: A61K 31/38 having sulfur as a ring hetero atom
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

The invention provides methods for treating an individual having a retinoid responsive disorder. In one embodiment, a method involves administering to the individual an effective amount of a selective CYP26B inhibitor, the selective CYP26B inhibitor having at least 10-fold selectivity for CYP26B relative to CYP26A. In another embodiment, a method involves administering to the individual an effective amount of a selective CYP26A inhibitor, the selective CYP26A inhibitor having a chemical formula set forth in the specification. The invention further provides screening methods for identifying a selective CYP26A inhibitor or selective CYP26B inhibitor.

Claims

1. A method for treating an individual having a retinoid responsive disorder, comprising administering to said individual an effective amount of a selective CYP26B inhibitor, wherein said selective CYP26B inhibitor has at least 10-fold selectivity for CYP26B relative to CYP26A.

2. The method of claim 1, wherein said retinoid responsive disorder is a skin disorder.

3. The method of claim 2, wherein said skin disorder is acne.

4. The method of claim 1, wherein said retinoid responsive disorder is a disorder selected from an autoimmune disorder, an inflammatory disorder, a proliferative disorder, a neurological disorder, an ocular disorder, and a pulmonary disorder.

5. The method of claim 1, wherein said inhibitor is administered peripherally.

6. The method of claim 5, wherein said inhibitor is administered orally.

7. The method of claim 1, wherein said individual is a human.

8. The method of claim 1, wherein said selective CYP26B inhibitor has at least 20-fold selectivity for CYP26B relative to CYP26A.

9. The method of claim 8, wherein said selective CYP26B inhibitor has at least 100-fold selectivity for CYP26B relative to CYP26A.

10. The method of claim 9, wherein said selective CYP26B inhibitor has at least 500-fold selectivity for CYP26B relative to CYP26A.

11. The method of claim 10, wherein said selective CYP26B inhibitor has at least 1000-fold selectivity for CYP26B relative to CYP26A.

12. The method of claim 1, wherein said selective CYP26B inhibitor has the formula:

13. The method of claim 1, wherein said selective CYP26B inhibitor has the formula:

14. The method of claim 1, wherein said selective CYP26B inhibitor has the formula:

15. A method for treating an individual having a retinoid responsive disorder, comprising administering to said individual an effective amount of a selective CYP26A inhibitor having the formula:

16. The method of claim 15, wherein said retinoid responsive disorder is a skin disorder.

17. The method of claim 15, wherein said retinoid responsive disorder is a disorder selected from the group consisting of an autoimmune disorder, an inflammatory disorder, a proliferative disorder, a neurological disorder, an ocular disorder, and a pulmonary disorder.

18. The method of claim 15, wherein said administering is oral administering.

19. The method of claim 16, wherein said skin disorder is acne.

20. A method for treating an individual having a retinoid responsive disorder, comprising administering to said individual an effective amount of a selective CYP26A inhibitor having the formula:

21. The method of claim 20, wherein said retinoid responsive disorder is a skin disorder.

22. The method of claim 20, wherein said retinoid responsive disorder is a disorder selected from the group consisting of an autoimmune disorder, an inflammatory disorder, a proliferative disorder, a neurological disorder, an ocular disorder, and a pulmonary disorder.

23. The method of claim 20, wherein said administering is oral administering.

24. The method of claim 21, wherein said skin disorder is acne.

25. A method for treating an individual having a retinoid responsive disorder, comprising administering to said individual an effective amount of a selective CYP26A inhibitor having the formula:

26. The method of claim 25, wherein said retinoid responsive disorder is a skin disorder.

27. The method of claim 25, wherein said retinoid responsive disorder is a disorder selected from the group consisting of an autoimmune disorder, an inflammatory disorder, a proliferative disorder, a neurological disorder, an ocular disorder, and a pulmonary disorder.

28. The method of claim 25, wherein said administering is oral administering.

29. The method of claim 26, wherein said skin disorder is acne.

30. A method for treating an individual having a retinoid responsive disorder, comprising administering to said individual an effective amount of a selective CYP26A inhibitor having the formula:

31. The method of claim 30, wherein said retinoid responsive disorder is a skin disorder.

32. The method of claim 30, wherein said retinoid responsive disorder is a disorder selected from the group consisting of an autoimmune disorder, an inflammatory disorder, a proliferative disorder, a neurological disorder, an ocular disorder, and a pulmonary disorder.

33. The method of claim 30, wherein said administering is oral administering.

34. The method of claim 31, wherein said skin disorder is acne.

35. A method for treating an individual having a retinoid responsive disorder, comprising administering to said individual an effective amount of a selective CYP26A inhibitor having the formula:

36. The method of claim 35, wherein said retinoid responsive disorder is a skin disorder.

37. The method of claim 35, wherein said retinoid responsive disorder is a disorder selected from the group consisting of an autoimmune disorder, an inflammatory disorder, a proliferative disorder, a neurological disorder, an ocular disorder, and a pulmonary disorder.

38. The method of claim 35, wherein said administering is oral administering.

39. The method of claim 36, wherein said skin disorder is acne.

40. A method for treating an individual having a retinoid responsive disorder, comprising administering to said individual an effective amount of a selective CYP26A inhibitor having the formula:

41. The method of claim 40, wherein said retinoid responsive disorder is a skin disorder.

42. The method of claim 40, wherein said retinoid responsive disorder is a disorder selected from the group consisting of an autoimmune disorder, an inflammatory disorder, a proliferative disorder, a neurological disorder, an ocular disorder, and a pulmonary disorder.

43. The method of claim 40, wherein said administering is oral administering.

44. The method of claim 41, wherein said skin disorder is acne.

45. A method for treating an individual having a retinoid responsive disorder, comprising administering to said individual an effective amount of a selective CYP26A inhibitor having the formula:

46. The method of claim 45, wherein said retinoid responsive disorder is a skin disorder.

47. The method of claim 45, wherein said retinoid responsive disorder is a disorder selected from the group consisting of an autoimmune disorder, an inflammatory disorder, a proliferative disorder, a neurological disorder, an ocular disorder, and a pulmonary disorder.

48. The method of claim 45, wherein said administering is oral administering.

49. The method of claim 46, wherein said skin disorder is acne.

50. A method for treating an individual having a retinoid responsive disorder, comprising administering to said individual an effective amount of a selective CYP26A inhibitor having the formula:

51. The method of claim 50, wherein said retinoid responsive disorder is a skin disorder.

52. The method of claim 50, wherein said retinoid responsive disorder is a disorder selected from the group consisting of an autoimmune disorder, an inflammatory disorder, a proliferative disorder, a neurological disorder, an ocular disorder, and a pulmonary disorder.

53. The method of claim 50, wherein said administering is oral administering.

54. The method of claim 51, wherein said skin disorder is acne.

55. A method for treating an individual having a retinoid responsive disorder, comprising administering to said individual an effective amount of a selective CYP26A inhibitor having the formula:

56. The method of claim 55, wherein said retinoid responsive disorder is a skin disorder.

57. The method of claim 55, wherein said retinoid responsive disorder is a disorder selected from the group consisting of an autoimmune disorder, an inflammatory disorder, a proliferative disorder, a neurological disorder, an ocular disorder, and a pulmonary disorder.

58. The method of claim 55, wherein said administering is oral administering.

59. The method of claim 56, wherein said skin disorder is acne.

60. A method for treating an individual having a retinoid responsive disorder, comprising administering to said individual an effective amount of a selective CYP26A inhibitor having the formula:

61. The method of claim 60, wherein said retinoid responsive disorder is a skin disorder.

62. The method of claim 60, wherein said retinoid responsive disorder is a disorder selected from the group consisting of an autoimmune disorder, an inflammatory disorder, a proliferative disorder, a neurological disorder, an ocular disorder, and a pulmonary disorder.

63. The method of claim 60, wherein said administering is oral administering.

64. The method of claim 61, wherein said skin disorder is acne.

65. A method for treating an individual having a retinoid responsive disorder, comprising administering to said individual an effective amount of a selective CYP26A inhibitor having the formula:

66. The method of claim 65, wherein said retinoid responsive disorder is a skin disorder.

67. The method of claim 65, wherein said retinoid responsive disorder is a disorder selected from the group consisting of an autoimmune disorder, an inflammatory disorder, a proliferative disorder, a neurological disorder, an ocular disorder, and a pulmonary disorder.

68. The method of claim 65, wherein said administering is oral administering.

69. The method of claim 66, wherein said skin disorder is acne.

70. A method for treating an individual having a retinoid responsive disorder, comprising administering to said individual an effective amount of a selective CYP26A inhibitor having the formula:

71. The method of claim 70, wherein said retinoid responsive disorder is a skin disorder.

72. The method of claim 70, wherein said retinoid responsive disorder is a disorder selected from the group consisting of an autoimmune disorder, an inflammatory disorder, a proliferative disorder, a neurological disorder, an ocular disorder, and a pulmonary disorder.

73. The method of claim 70, wherein said administering is oral administering.

74. The method of claim 71, wherein said skin disorder is acne.