Composition and Methods of Use of Small Molecules as Binding Ligands for the Modulation of Proprotein Convertase Subtilisin/Kexin Type 9(PCSK9) Protein Activity
Thomas E Barta,Jonathan W. Bourne,Kyle D. Monroe,Michael M. Muehlemann
申请号：
US16380414
公开号：
US20190358248A1
申请日:
2019.04.10
申请国别(地区):
US
年份:
2019
代理人:
摘要：
This invention is related to the field of PCSK9 biology and the composition and methods of use of small molecule ligands for modulation of PCSK9 biological activity. In particular, the invention provides compositions of small molecule compounds that modulate circulating levels of low density lipoproteins by altering the conformation of the protein PCSK9. Binding these small molecule ligands to PCSK9 alters the conformation of the protein, modifying the interaction between PCSK9 and an endogenous low density lipoprotein receptor, and can lead to reduced or increased levels of circulating LDL-cholesterol. High LDL cholesterol levels are associated with increased risk for heart disease. Low LDL-cholesterol levels may be problematic in other conditions, such as liver dysfunction； thus, there is also utility for small molecule ligands that can raise LDL levels.
