Compositions and treatments for modulating kinase and/or HMG-CoA reductase
The present invention provides compositions of matter, kits and methods for their use in the treatment of kinase-related conditions and/or HMG-CoA reductase-related conditions. In particular, the invention provides compositions for treating immuno-compromised and/or cardiovascular conditions in an animal subject by modulating one or more MAP kinase(s) and/or HMG-CoA reductase, as well as providing formulations and modes of administering such compositions. The invention further provides methods for the rational design of modulators of MAP kinases, HMG-CoA reductase, or both for use in the practice of the present invention.
1 . A method of activating a MAP kinase comprising administering an effective amount of a composition comprising a statin lactone.
2 . The method as recited in claim 1 wherein said activation occurs in a cell other than a brain cell.
3 . The method as recited in claim 1 wherein said activating occurs by direct activation.
4 . The method as recited in claim 1 wherein said activating does not occur via a growth factor.
5 . The method as recited in claim 1 wherein said activating is not reversed by addition of at least one compound selected from farnesyl pyrophosphate, geranylgeranyl pyrophosphate and mevalonte.
6 . The method as recited in claim 1 wherein said activating is not reversed by addition of a downstream product of mevalonate.
7 . The method as recited in claim 1 wherein said MAP kinase is a p38 MAP kinase.
8 . The method as recited in claim 1 wherein said MAP kinase is a p38α MAP kinase.
9 . The method as recited in claim 8 wherein said statin lactone is simvastatin lactone.
10 . The method as recited in claim 8 wherein said statin lactone is cerivastatin lactone.
11 . The method as recited in claim 8 wherein said statin lactone is fluvastatin lactone.
12 . The method as recited in claim 8 wherein said statin lactone is lovastatin lactone.
13 . The method as recited in claim 8 wherein said statin lactone is mevastatin lactone.
14 . The method as recited in claim 8 wherein said statin lactone is not atorvastatin lactone, rosuvastatin lactone, nor pitavastatin lactone.
15 . The method as recited in claim 1 wherein said MAP kinase is a p38β MAP kinase.
16 . The method as recited in claim 15 wherein said statin lactone is simvastatin lactone.
17 . The method as recited in claim 15 wherein said statin lactone is cerivastatin lactone.
18 . The method as recited in claim 15 wherein said statin lactone is fluvastatin lactone.
19 . The method as recited in claim 15 wherein said statin lactone is atorvastatin lactone.
20 . The method as recited in claim 15 wherein said statin lactone is not rosuvastatin lactone.
21 . The method as recited in claim 1 wherein said MAP kinase is a p38γ MAP kinase.
22 . The method as recited in claim 21 wherein said statin lactone is simvastatin lactone.
23 . The method as recited in claim 21 wherein said statin lactone is cerivastatin lactone.
24 . The method as recited in claim 21 wherein said statin lactone is rosuvastatin lactone.
25 . The method as recited in claim 21 wherein said statin lactone is atorvastatin lactone.
26 . The method as recited in claim 21 wherein said statin lactone is pitavastatin lactone.
27 . The method as recited in claim 21 wherein said stain lactone is not fluvastatin lactone.
28 . The method as recited in claim 1 wherein said MAP kinase is a p38δ MAP kinase.
29 . The method as recited in claim 28 wherein said statin lactone is simvastatin lactone.
30 . The method as recited in claim 28 wherein said statin lactone is cerivastatin lactone.
31 . The method as recited in claim 28 wherein said statin lactone is rosuvastatin lactone.
32 . The method as recited in claim 28 wherein said statin lactone is atorvastatin lactone.
33 . The method as recited in claim 28 wherein said statin lactone is fluvastatin lactone.
34 . The method as recited in claim 1 wherein said composition activates at least two MAP kinases.
35 . The method as recited in claim 34 wherein said at least two MAP kinases are selected from a p38α MAP kinase, a p38β MAP kinase, a p38γ MAP kinase, a p38δ MAP kinase, and a p42 MAP kinase.
36 . The method as recited in claim 34 wherein said statin lactone is at least one lactone selected from simvastatin lactone, cerivastatin lactone, fluvastatin lactone, rosuvastatin lactone, and atorvastatin lactone.
37 . The method as recited in claim 1 wherein said MAP kinase is a JNK.
38 . The method as recited in claim 37 wherein said activating facilitates a Fas apoptotic pathway.