METHODS OF IDENTIFYING ACTIVATORS OF LYN KINASE

1 . A method of identifying an activator of lyn kinase comprising:

preincubating a test compound in the presence of lyn kinase;

adding ATP and substrate to the lyn kinase and test compound;

incubating the test compound, lyn kinase, ATP, and substrate; and

measuring the phosphorylation level of the substrate, whereby an increase in the phosphorylation level of the substrate indicates that the test compound is an activator of lyn kinase.

2 . The method of claim 1 wherein the test compound is preincubated in the presence of lyn kinase from about 5 minutes to about 120 minutes.

3 - 5 . (canceled)

6 . The method of claim 1 wherein the test compound is preincubated in the presence of lyn kinase at about 0° C. to about 30° C.

7 - 8 . (canceled)

9 . The method of claim 1 wherein the concentration of the lyn kinase is from about 10 ng/ml to about 500 ng/ml.

10 . (canceled)

11 . The method of claim 1 wherein the concentration of ATP is from about 5 μM to about 25 μM.

12 . (canceled)

13 . The method of claim 1 wherein the ATP is radiolabelled.

14 . The method of claim 1 wherein the substrate is a protein or peptide that comprises a tyrosine.

15 . The method of claim 1 wherein the substrate is a synthetic FRET peptide comprising a tyrosine.

16 . The method of claim 1 wherein the test compound, lyn kinase, ATP, and substrate are incubated at about room temperature from about 5 minutes to about 90 minutes.

17 - 19 . (canceled)

20 . The method of claim 13 wherein measuring the phosphorylation level of the substrate comprises quantitatively or qualitatively measuring the radiolabelled substrate.

21 . The method of claim 15 wherein measuring the phosphorylation level of the substrate comprises quantitatively or qualitatively measuring the fluorescence of the synthetic FRET peptide substrate.

22 . The method of claim 1 wherein the incubation of the test compound, lyn kinase, ATP, and substrate takes place in the presence of from about 0.05% to about 0.25% bovine serum albumin, from about 0.5 mM to about 2.5 mM dithiothreitol, from about 0.05% to about 0.25% bovine serum albumin and from about 0.5 mM to about 2.5 mM dithiothreitol, or from about 0.05% to about 0.25% β-mercaptoethanol.

23 . The method of claim 1 wherein the incubation of the test compound, lyn kinase, ATP, and substrate takes place in the presence of from about 0.05% to about 0.25% β-mercaptoethanol.

24 . The method of claim 1 wherein the incubation of the test compound, lyn kinase, ATP, and substrate takes place in the presence of about 0.1% β-mercaptoethanol.

25 . The method of claim 1 wherein:

the test compound is preincubated in the presence of lyn kinase from about 5 minutes to about 120 minutes;

the test compound is preincubated in the presence of lyn kinase at about 0° C. to about 30° C.; and

the test compound, lyn kinase, ATP, and substrate are incubated at about room temperature from about 5 minutes to about 90 minutes, in the presence of from about 0.05% to about 0.25% β-mercaptoethanol.

26 - 28 . (canceled)

29 . The method of claim 1 wherein the test compound is a compound of formula II

wherein:

R 1 is an alkyl group;

X is a halogen;

Y is O, S, or NH;

Z is O or S;

n is an integer from 0 to 5 and m is 0 or 1, wherein m+n is less than or equal to 5.

30 - 37 . (canceled)

38 . The method of claim 29 wherein the test compound is

39 . A kit comprising lyn kinase, ATP, substrate, and instructions for carrying out the method of claim 1 .

40 . (canceled)

41 . A composition comprising a first compound of formula II:

wherein

each of R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , and R 7 are independently a hydrogen, alkoxy, alkyl, alkenyl, alkynyl, aryl, aryloxy, benzyl, cycloalkyl, halogen, heteroaryl, heterocycloalkyl, —CN, —OH, —NO 2 , —CF 3 , —CO 2 H, —CO 2 alkyl, or —NH 2 ;

R 8 is alkyl or hydrogen;

X is O, S, NH, or N-alkyl; and

Z is O or S; or a pharmaceutically acceptable salt thereof; and

one or more second compounds, or pharmaceutically acceptable salt thereof, selected from the compounds listed in Table I.

42 . The composition of claim 41 wherein the first compound is of formula II

wherein:

R 1 is an alkyl group;

X is a halogen;

Y is O, S, or NH;

Z is O or S; and

n is an integer from 0 to 5 and m is 0 or 1, wherein m+n is less than or equal to 5.

43 . A method of treating diabetes in a human comprising administering to the human in need thereof a therapeutically effective amount of a composition of claim 41 .

44 . A pharmaceutical composition comprising a compound of formula II

wherein:

R 1 is an alkyl group;

X is a halogen;

Y is O, S, or NH;

Z is O or S; and

n is an integer from 0 to 5 and m is 0 or 1, wherein m+n is less than or equal to 5, or a pharmaceutically acceptable salt thereof; and

rosiglitazone.

45 . The pharmaceutical composition of claim 44 wherein the compound of formula II is

46 . The pharmaceutical composition of claim 44 wherein the compound of formula II is