Cholesterol-Lowering Compound Targeting LBR and EBP Selectively
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current cholesterol-lowering drugs pose risks and contraindications, necessitating the development of safer alternatives for managing high cholesterol levels, particularly in conditions like hypercholesterolemia.
Innovation Solution
Compound 1, an inhibitor of multiple enzymes in the cholesterol biosynthesis pathway, reduces cholesterol levels in a dose-dependent manner by inhibiting LBR/TM7SF2 and EBP, leading to the accumulation of 7-dehydrocholesterol, thereby lowering elevated plasma cholesterol levels.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If current cholesterol lowering drugs are used, then cholesterol levels are reduced, but risks and contraindications increase
Solution Approach 1:
The patent employs parameter changes by modifying the biochemical parameters of cholesterol metabolism through inhibition of specific enzymes (LBR and EBP) in the cholesterol biosynthesis pathway. This approach reduces cholesterol levels by altering the metabolic pathway parameters rather than using conventional drugs with known safety issues, thereby achieving lipid reduction with a potentially safer profile
2Quantity of substance
If Compound 1 is used to lower cholesterol, then peripheral cholesterol levels decrease, but potential off-target effects may occur
Solution Approach 1:
The patent applies local quality by demonstrating that Compound 1 selectively reduces cholesterol in peripheral tissues while maintaining cholesterol levels in the central nervous system. This selective action is achieved through the blood-brain barrier properties of the compound, allowing different tissue compartments to maintain different cholesterol characteristics - peripheral tissues experience cholesterol reduction while the CNS maintains its cholesterol homeostasis
Solution Approach 2:
The patent uses the blood-brain barrier as an intermediary mechanism that protects the central nervous system from the cholesterol-lowering effects of Compound 1. This natural barrier acts as a mediator that allows the compound to reach peripheral tissues while preventing its penetration into the CNS, thereby reducing off-target effects and enabling selective peripheral cholesterol reduction
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
Compound 1 effectively decreases peripheral cholesterol levels in humans without significantly affecting central nervous system cholesterol, offering a safer alternative for treating hypercholesterolemia and associated conditions.
Implementation Method 1
Compound 1, whose structure is shown below, is an inhibitor of multiple enzymes in the cholesterol biosynthesis pathway, including LBR/TM7SF2 and EBP
Data Source
Figure 1
Figure 2
Figure 3
AI summary
Disclosed is a method of lowering elevated cholesterol plasma levels in a subject. Also disclosed is a method of treating hypercholesterolemia in a subject. The methods comprise administering to the subject in the absence of a cholesterol lowering drug an effective amount of Compound 1 or pharmaceutically acceptable salt thereof.