Methods, compositions, and kits for treating and/or preventing a side effect associated with radiation and/or chemotherapy exposure

1. A method of treating and/or preventing one or more side effects associated with chemotherapy exposure in a subject during and/or following chemotherapy exposure, the method comprising:

administering to the subject prior to, during, or after chemotherapy exposure an active agent at a loading dose in an amount of about 0.05 mg/kg to about 1 mg/kg times the activity equivalent of BMX-001;

wherein the active agent is a meso-substituted metalloporphyrin.

2. The method of claim 1 , wherein the active agent is a superoxide dismutase (SOD) mimetic.

3. The method of claim 1 , wherein the active agent is a compound of Formula I:

wherein:

each R is independently selected from a substituted or unsubstituted aryl, heteroaryl, cycloalkyl, or heterocycloalkyl;

each A is an independently selected from a hydrogen, an electron-withdrawing group, or an electron donating group;

M is a metal; and

Z— is a counterion;

or a pharmaceutically acceptable salt thereof.

4. The method of claim 1 , wherein the active agent has a structure of Formula A1:

wherein:

each R is independently C1-12 alkyl or C1-C12 alkoxyalkyl;

each A is, independently, hydrogen or an electron withdrawing group;

M is a metal selected from the group consisting of manganese, iron, copper, cobalt, and nickel; and

Z— is a counterion;

or a pharmaceutically acceptable salt thereof.

5. The method of claim 1 , wherein the active agent has a structure of Formula B1:

wherein:

each R is independently C1-12 alkyl or C1-C12 alkoxyalkyl;

each A is, independently, hydrogen or an electron withdrawing group;

M is a metal selected from the group consisting of manganese, iron, copper, cobalt, and nickel; and

Z— is a counterion;

or a pharmaceutically acceptable salt thereof.

6. The method of claim 1 , wherein said active agent has a structure of Formula C1:

wherein:

each R is, independently, hydrogen or —(CH 2 ) m CH 2 OX;

m is 1 or 2;

X is C1-12 alkyl;

each A is, independently, hydrogen or an electron withdrawing group;

M is a metal selected from the group consisting of manganese, iron, copper, cobalt, and nickel; and

Z— is a counterion;

or a pharmaceutically acceptable salt thereof.

7. The method of claim 1 ,

wherein the active agent has the structure:

wherein Z − is a counterion; or a pharmaceutically acceptable salt thereof.

8. The method of claim 1 , wherein the loading dose is administered to the subject in an amount of about 0.1 mg/kg to about 0.6 mg/kg or about 0.1 mg/kg to about 0.6 mg/kg times the activity equivalent of BMX-001.

9. The method of claim 1 , wherein the loading dose is administered to the subject at about 30 minutes to about 4 days prior to the subject being exposed to the chemotherapy.

10. The method of claim 1 , wherein the loading dose is administered to the subject during and/or after the subject is exposed to the chemotherapy.

11. The method of claim 1 , further comprising administering to the subject the active agent at a maintenance dose in an amount that is about 25% to about 75% less than the amount of the active agent in the loading dose.

12. The method of claim 1 , wherein the amount of active agent administered to the subject in the loading dose is about 5 mg to about 50 mg.

13. The method of claim 1 , wherein the loading dose is only administered one time as the initial dose.

14. The method of claim 1 , further comprising administering to the subject a maintenance dose, wherein the amount of the active agent administered to the subject in the maintenance dose is about 5 mg/week to about 50 mg/week times the activity equivalent of BMX-001.

15. The method of claim 1 , further comprising administering to the subject a maintenance dose, wherein the maintenance dose is administered to the subject two or three times per week.

16. The method of claim 1 , further comprising administering to the subject a maintenance dose, wherein the maintenance dose is administered two or three times a week after an initial chemotherapy exposure.

17. The method of claim 1 , further comprising administering to the subject a maintenance dose, wherein the maintenance dose is administered every two or three days for 1 to 8 weeks after a final chemotherapy exposure.

18. The method of claim 1 , wherein the subject is further receiving radiation therapy.

19. The method of claim 18 , wherein the method treats and/or prevents radiation-induced normal tissue injury in the subject.

20. The method of claim 18 , wherein the method treats and/or prevents one or more side effects associated with the radiation therapy.

21. A method of treating and/or preventing one or more side effects associated with radiation and/or chemotherapy exposure in a subject during and/or following radiation and/or chemotherapy exposure, the method comprising:

administering to the subject prior to, during, or after radiation and/or chemotherapy exposure an active agent at a loading dose in an amount of about 0.05 mg/kg to about 1 mg/kg times the activity equivalent of BMX-001;

wherein the active agent is a meso-substituted metalloporphyrin, and

wherein the loading dose is only administered one time as an initial dose.

22. The method of claim 21 , wherein the active agent is a compound of Formula I:

wherein:

each R is independently selected from a substituted or unsubstituted aryl, heteroaryl, cycloalkyl, or heterocycloalkyl;

each A is an independently selected from a hydrogen, an electron-withdrawing group, or an electron donating group;

M is a metal; and

Z— is a counterion;

or a pharmaceutically acceptable salt thereof.

23. The method of claim 21 , wherein the active agent has a structure of Formula A1:

wherein:

each R is independently C1-12 alkyl or C1-C12 alkoxyalkyl;

each A is, independently, hydrogen or an electron withdrawing group;

M is a metal selected from the group consisting of manganese, iron, copper, cobalt, and nickel; and

Z— is a counterion;

or a pharmaceutically acceptable salt thereof.

24. The method of claim 21 , wherein the active agent has a structure of Formula B1:

wherein:

each R is independently C1-12 alkyl or C1-C12 alkoxyalkyl;

each A is, independently, hydrogen or an electron withdrawing group;

M is a metal selected from the group consisting of manganese, iron, copper, cobalt, and nickel; and

Z— is a counterion; or a pharmaceutically acceptable salt thereof.

25. The method of claim 21 , wherein the active agent has the structure:

wherein Z − is a counterion, or a pharmaceutically acceptable salt thereof.

26. The method of claim 21 , wherein the loading dose is administered to the subject in an amount of about 0.1 mg/kg to about 0.6 mg/kg or about 0.1 mg/kg to about 0.6 mg/kg times the activity equivalent of BMX-001.

27. The method of claim 21 , wherein the loading dose is administered to the subject at about 30 minutes to about 4 days prior to the subject being exposed to the radiation and/or chemotherapy.

28. The method of claim 21 , wherein the loading dose is administered to the subject during and/or after the subject is exposed to the radiation and/or chemotherapy.

29. The method of claim 21 , further comprising administering to the subject the active agent at a maintenance dose in an amount that is about 25% to about 75% less than the amount of the active agent in the loading dose.

30. The method of claim 21 , wherein the amount of active agent administered to the subject in the loading dose is about 5 mg to about 50 mg.

31. The method of claim 21 , further comprising administering to the subject a maintenance dose, wherein the amount of active agent administered to the subject in the maintenance dose is about 5 mg/week to about 50 mg/week times the activity equivalent of BMX-001.

32. The method of claim 21 , further comprising administering to the subject a maintenance dose, wherein the maintenance dose is administered to the subject two or three times per week.

33. The method of claim 21 , further comprising administering to the subject a maintenance dose, wherein the maintenance dose is administered two or three times a week after an initial radiation and/or chemotherapy exposure.

34. The method of claim 21 , further comprising administering to the subject a maintenance dose, wherein the maintenance dose is administered every two or three days for 1 to 8 weeks after a final radiation and/or chemotherapy exposure.

35. The method of claim 21 , wherein the method treats or prevents one or more side effects associated with radiation exposure in a subject during and/or following radiation exposure and the method comprises administering to the subject the active agent prior to, during, or after the radiation exposure.

36. The method of claim 21 , wherein the method treats or prevents one or more side effects associated with chemotherapy exposure in a subject during and/or following chemotherapy exposure and the method comprises administering to the subject the active agent prior to, during, or after the chemotherapy exposure.

37. A method of treating and/or preventing one or more side effects associated with radiation exposure in a subject during and/or following radiation exposure, optionally in combination with chemotherapy exposure, the method comprising:

administering to the subject prior to, during, or after radiation exposure, and optionally chemotherapy exposure, an active agent at a loading dose in an amount of about 0.05 mg/kg to about 1 mg/kg times the activity equivalent of BMX-001;

wherein the active agent is a meso-substituted metalloporphyrin, and

wherein the radiation exposure comprises at least one radiation treatment that is administered 5 days a week for 1 to 10 weeks.

38. The method of claim 37 , wherein the active agent is a compound of Formula I:

wherein:

each R is independently selected from a substituted or unsubstituted aryl, heteroaryl, cycloalkyl, or heterocycloalkyl;

each A is an independently selected from a hydrogen, an electron-withdrawing group, or an electron donating group;

M is a metal; and

Z— is a counterion;

or a pharmaceutically acceptable salt thereof.

39. The method of claim 37 , wherein the active agent has a structure of Formula A1:l

wherein:

each R is independently C1-12 alkyl or C1-C12 alkoxyalkyl;

each A is, independently, hydrogen or an electron withdrawing group;

M is a metal selected from the group consisting of manganese, iron, copper, cobalt, and nickel; and

Z— is a counterion;

or a pharmaceutically acceptable salt thereof.

40. The method of claim 37 , wherein the active agent has a structure of Formula B1:

wherein:

each R is independently C1-12 alkyl or C1-C12 alkoxyalkyl;

each A is, independently, hydrogen or an electron withdrawing group;

M is a metal selected from the group consisting of manganese, iron, copper, cobalt, and nickel; and

Z— is a counterion;

or a pharmaceutically acceptable salt thereof.

41. The method of claim 37 , wherein the active agent has the structure:

wherein Z − is a counterion; or

a pharmaceutically acceptable salt thereof.

42. The method of claim 37 , wherein the loading dose is administered to the subject in an amount of about 0.1 mg/kg to about 0.6 mg/kg or about 0.1 mg/kg to about 0.6 mg/kg times the activity equivalent of BMX-001.

43. The method of claim 37 , wherein the loading dose is administered to the subject at about 30 minutes to about 4 days prior to the subject being exposed to the radiation and optionally chemotherapy.

44. The method of claim 37 , wherein the loading dose is administered to the subject during and/or after the subject is exposed to the radiation and optionally chemotherapy.

45. The method of claim 37 , further comprising administering to the subject the active agent at a maintenance dose in an amount that is about 25% to about 75% less than the amount of the active agent in the loading dose.

46. The method of claim 37 , wherein the amount of active agent administered to the subject in the loading dose is about 5 mg to about 50 mg.

47. The method of claim 37 , wherein the loading dose is only administered one time as the initial dose.

48. The method of claim 27 , further comprising administering to the subject a maintenance dose, wherein the amount of active agent administered to the subject in the maintenance dose is about 5 mg/week to about 50 mg/week times the activity equivalent of BMX-001.

49. The method of claim 37 , further comprising administering to the subject a maintenance dose, wherein the maintenance dose is administered to the subject two or three times per week.

50. The method of claim 37 , further comprising administering to the subject a maintenance dose, wherein the maintenance dose is administered two or three times a week after an initial radiation and/or chemotherapy exposure.

51. The method of claim 37 , further comprising administering to the subject a maintenance dose, wherein the maintenance dose is administered every two or three days for 1 to 8 weeks after a final radiation and/or chemotherapy exposure.

52. The method of claim 37 , wherein the method treats or prevents one or more side effects associated with radiation and chemotherapy exposure in a subject during and/or following radiation and chemotherapy exposure and the method comprises administering to the subject the active agent prior to, during, or after the radiation and chemotherapy exposure.