METHOD FOR IDENTIFYING COMPOUNDS THAT ACT AS INSULIN-SENSITIZERS

1 . A method of identifying a lead compound which acts as an insulin-sensitizer, comprising:

subjecting test compounds to screening using an adipogenesis assay;

determining whether the test compounds caused formation of adipocytes in the adipogenesis assay;

identifying the test compounds that caused the formation of adipocytes by more than 5 times a vehicle control as actives;

subjecting the compounds identified as actives to second screening using insulin resistant adipocytes;

determining whether the compounds enhance glucose uptake in the insulin resistant adipocytes; and

identifying the compound, which enhances glucose uptake in the insulin resistant adipocytes by more than 50% above than that enhanced by insulin as a lead compound.

2 . (canceled)

3 . The method according to claim 1 , wherein the screening using the adipogenesis assay comprises screening against 3T3-L1 adipocytes.

4 . (canceled)

5 . The method according to claim 1 , wherein the screening using insulin resistant adipocytes comprises screening against dexamethasone treated 3T3-L1 adipocytes.

6 . The method of claim 1 , further comprising the step of screening the lead compound for activity in an animal model of insulin resistance, comprising measuring plasma glucose levels in genetically diabetic db/db BL/6J mice.

7 . The method of claim 1 , further comprising the step of screening the lead compounds for activity in an animal model of insulin resistance comprising measuring food intake and body weight gain in diet-induced obese C57Bl6/J mice.

8 . A method for the treatment of disorders caused by insulin resistance to glucose uptake and disorders related thereto comprising administering to a mammal in need thereof a therapeutically effective amount of a compound, wherein said compound is identified as a lead compound by a method of identifying a lead compound which act as an insulin-sensitizer, wherein said method comprising:

subjecting test compounds to screening using an adipogenesis assay;

determining whether the test compounds caused formation of adipocytes in the adipogenesis assay;

identifying the test compounds that caused the formation of adipocytes by more than 5 times a vehicle control as actives;

subjecting the compounds identified as actives to second screening using insulin resistant adipocytes;

determining whether the compounds enhance glucose uptake in the insulin resistant adipocytes; and

identifying the compound, which enhances glucose uptake in the insulin resistant adipocytes by more than 50% above than that enhanced by insulin, as a lead compound.

9 . The method of treatment according to claim 8 , wherein the compound is:

2-{4-[2-(tert-Butoxycarbonyl-methyl-amino)-ethoxy]-benzyl}-2-methoxy-malonic acid dimethyl ester;

3-{4-[2-(tert-Butoxycarbonyl-methyl-amino)-ethoxy]-phenyl}-2-methoxy-propionic acid;

3-{5-[2-(Benzooxazol-2-yl-methyl-amino)-ethylamino]-1-oxo-1,3-dihydro-isoindol-2-yl}-propionic acid ethyl ester;

2,4-Dichloro-N-[5-chloro-6-(isoquinolin-3-yloxy)pyridin-3-yl]-benzenesulfonamide;

N-{6-[4-(4-Acetyl-piperazin-1-yl)-phenoxy]-5-chloro-pyridin-3-yl}-2,4-dichloro-benzenesulfonamide; or

N-[5-Chloro-6-(quinolin-3-yloxy)-pyridine-3-yl]-4-methoxy-benzene sulfonamide;

or a pharmaceutically acceptable salt or solvate or crystalline form thereof.

10 . The method of treatment according to claim 8 , wherein the disorders caused by insulin resistance to glucose uptake comprises Type 2 diabetes, obesity, glucose intolerance, dyslipidemia, hyperinsulinemia, atherosclerotic disease, polycystic ovary syndrome, coronary artery disease, hypertension, aging, non alcoholic fatty liver disease, infections, cancer and stroke.

11 . (canceled)

12 . The method of treatment according to claim 10 , wherein the disorder caused by insulin resistance to glucose uptake is type 2 diabetes.

13 . The method of treatment according to claim 10 , wherein the disorder caused by insulin resistance to glucose uptake is obesity.

14 . The method of treatment according to claim 10 , wherein the disorder caused by insulin resistance to glucose uptake is dyslipidemia.