This invention is related to the field of PCSK9 biology and the composition and methods of use of small organic compounds as ligands for modulation of PCSK9 biological activity. In particular, the invention provides compositions of small organic compounds that modulate circulating levels of low density lipoproteins by altering the conformation of the protein PCSK9. Binding these small organic compound 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 organic compound ligands that can raise LDL levels.
这项发明涉及PCSK9
生物学领域,以及小有机化合物作为调节PCSK9
生物活性的配方和使用方法。具体而言,该发明提供了调节低密度脂蛋白循环
水平的小有机化合物组合物,通过改变蛋白质PCSK9的构象来实现。将这些小有机化合物
配体结合到PCSK9上会改变蛋白质的构象,修改PCSK9与内源性低密度脂蛋白受体之间的相互作用,从而导致循环LDL
胆固醇水平降低或增加。高LDL
胆固醇水平与心脏疾病风险增加相关。低LDL
胆固醇水平可能在其他疾病情况下有问题,比如肝功能障碍;因此,开发能够提高LDL
水平的小有机化合物
配体也具有实用性。