Treatment of TNF- alpha cytotoxicity
Provided herein is technology relating to treating and/or ameliorating TNFα cytotoxicity and particularly, but not exclusively, to compositions, methods, and kits for specifically modulating BCL-2-associated death promoter (BAD) activity, for example, by modulating the activity of Src and/or p190GAP.
1. A composition comprising a compound according to the structure
wherein one or more of R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , or R 10 is a deuterium.
2. The composition of claim 1 wherein each of R 2 , R 3 , R 7 , and R 8 is a deuterium.
3. The composition of claim 1 wherein each of R 2 and R 3 is a deuterium.
4. The composition of claim 1 wherein each of R 9 and R 10 is a deuterium.
5. The composition of claim 1 wherein each of R 4 , R 5 , and R 6 is a deuterium.
6. The composition of claim 1 wherein each of R 7 and R 8 is a deuterium.
7. The composition of claim 1 wherein each of R 2 , R 3 , R 7 , R 8 , R 9 , and R 10 is a deuterium.
8. The composition of claim 1 wherein R 1 is a deuterium.
9. The composition of claim 1 wherein each of R 4 , R 5 , R 6 , R 9 , and R 10 is a deuterium.
10. The composition of claim 1 wherein each of R 1 , R 9 , and R 10 is a deuterium.
11. The composition of claim 1 wherein each of R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , and R 10 is a deuterium.
12. The composition of claim 1 wherein each of R 1 , R 4 , R 5 , R 6 , R 9 , and R 10 is a deuterium.
13. The composition of claim 1 wherein each of R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , and R 10 is a deuterium.
14. A method for reducing TNFα cytotoxicity in a subject, the method comprising administering to the subject a deuterated compound having a structure according to
15. The method of claim 14 wherein:
a) one or more of R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , or R 10 is a deuterium;
b) each of R 2 , R 3 , R 7 , and R 8 is a deuterium;
c) each of R 2 and R 3 is a deuterium;
d) each of R 9 and R 10 is a deuterium;
e) each of R 4 , R 5 , and R 6 is a deuterium;
f) each of R 7 and R 8 is a deuterium;
g) each of R 2 , R 3 , R 7 , R 8 , R 9 , and R 10 is a deuterium;
h) R 1 is a deuterium;
i) each of R 4 , R 5 , R 6 , R 9 , and R 10 is a deuterium;
j) each of R 1 , R 9 , and R 10 is a deuterium;
k) each of R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , and R 10 is a deuterium;
l) each of R 1 , R 4 , R 5 , R 6 , R 9 , and R 10 is a deuterium; and/or
m) each of R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , and R 10 is a deuterium in a structure according to
16. A pharmaceutical composition comprising a composition according to claim 1 .
17. The pharmaceutical composition of claim 16 formulated for administration to a human.
18. The method of claim 14 further comprising testing the subject for a microbial infection, sepsis, apoptosis, tissue or organ damage, rheumatoid arthritis, amyloid-beta, Alzheimer's disease, activation of Src, inflammatory disease, autoimmune disease, cancer, actin depolymerization, or transplant rejection.
19. The method of claim 18 further comprising a second administering of said compound to said subject.
20. The method of claim 14 wherein testing said subject comprises testing a sample from said subject.