THYROID HORMONE RECEPTOR AGONIST AND USE THEREOF
A thyroid hormone receptor agonist and its use in the treatment of a disease associated thyroid hormone receptor beta are described. The compound can be effective in lowering cholesterol with minimum or no adverse effects on the heart or thyroid hormone axis.
1 . A compound having a structure:
or a pharmaceutically acceptable salt thereof
2 . A pharmaceutical composition comprising the compound of claim 1 and a pharmaceutically acceptable excipient.
3 . A method for the treatment of a disease that is associated with thyroid hormone receptor β, comprising administering an effective amount of the compound of claim 1 to a subject in need thereof.
4 . The method of claim 3 , wherein the disease is selected from the group consisting of obesity, hyperlipidemia, hypercholesterolemia and diabetes, non-alcoholic fatty liver disease, NASH (nonalcoholic steatohepatitis), atherosclerosis, cardiovascular diseases, hypothyroidism, and thyroid cancer.
5 . A method of agonizing thyroid hormone receptor β, comprising contacting the thyroid hormone receptor β with an effective amount of the compound of claim 1 to a subject in need thereof.
6 . A method for lowering cholesterol levels comprising administering an effective amount of the compound of claim 1 to a subject in need thereof.
7 . A method for lowering triglyceride levels comprising administering an effective amount of the compound of claim 1 to a subject in need thereof.
8 . A method of preventing or treating a metabolic disease comprising administering to a subject in need thereof a pharmaceutically effective amount of the compound of claim 1 .
9 . The method of claim 8 , wherein the metabolic disease is selected from the group consisting of obesity, hypercholesterolemia, hyperlipidemia, atherosclerosis, coronary heart disease, and hypertension.
10 . The method of claim 3 , further comprising administering an additional therapeutic agent.
11 . The method of claim 3 , wherein the compound has a plasma half-life of less than 6 hours.
12 . The method of claim 3 , wherein the LDL level of the subject is reduced by at least 10% post administration compared to pre-administration level.
13 . The method of claim 3 , wherein the LDL level of the subject is reduced by at least 20% post administration compared to pre-administration level.
14 . The method of claim 3 , wherein the triglyceride level of the subject is reduced by at least 10% post administration compared to pre-administration level.
15 . The method of claim 3 , wherein the triglyceride level of the subject is reduced by at least 20% post administration compared to pre-administration level.
16 . The method of claim 3 , wherein the level of total T4 in the subject has a change of less than 50% post administration compared to pre-administration level.
17 . The method of claim 3 , wherein the level of total T3 in the subject has a change of less than 50% post administration compared to pre-administration levels.
18 . The method of claim 3 , wherein the level of thyroid-stimulating hormone (THS) in the subject has a change of less than 50% post administration compared to pre-administration level.
19 . The method of claim 3 , wherein the compound is administered parenterally.
20 . The method of claim 3 , wherein the compound is administered orally.