KHK Inhibitor Composition for Balanced Tissue Distribution
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current pharmacotherapies for metabolic syndrome and associated comorbidities lack effective inhibitors for ketohexokinase (KHK), leading to unregulated fructose metabolism, which contributes to insulin resistance, metabolic dysfunction, and tissue damage, with existing KHK inhibitors posing risks of tissue asymmetry, drug-drug interactions, and toxicity.
Innovation Solution
Development of novel KHK inhibitors with specific chemical structures, including heterocyclic moieties and cycloalkyl groups, designed to provide equal tissue distribution, high target engagement, and improved pharmacokinetics, reducing off-target liabilities and toxicity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing KHK inhibitors are used to regulate fructose metabolism, then metabolic dysfunction is addressed, but tissue asymmetry and toxicity occur
Solution Approach 1:
The patent modifies molecular parameters of KHK inhibitors by introducing specific heterocyclic moieties and cycloalkyl groups with defined substitution patterns, thereby changing the pharmacokinetic and pharmacodynamic parameters to achieve equal tissue distribution and reduced toxicity while maintaining fructose metabolism regulation
Solution Approach 2:
The patent introduces specific local structural features including heterocyclic rings with 1-3 heteroatoms and cycloalkyl groups with particular substituents at defined positions, creating local molecular quality differences that enable selective tissue distribution and reduced off-target effects while maintaining KHK inhibition activity
2Reliability
If existing KHK inhibitors are used to treat metabolic syndrome, then insulin resistance is addressed, but drug-drug interactions occur
Solution Approach 1:
The patent changes molecular parameters by incorporating specific heterocyclic and cycloalkyl structures with controlled substitution patterns, thereby modifying metabolic pathways and transport characteristics to reduce drug-drug interactions while maintaining therapeutic effect on insulin resistance
Solution Approach 2:
The patent introduces intermediary structural elements (heterocyclic moieties and cycloalkyl groups) that mediate between the core KHK inhibition function and the pharmacokinetic properties, allowing the drug to achieve therapeutic effect while minimizing interactions with other drugs through controlled tissue distribution and metabolic pathways
3Reliability
If conventional KHK inhibitors are developed, then fructose metabolism is regulated, but off-target liabilities increase
Solution Approach 1:
The patent segments the molecular structure into distinct functional modules: a core KHK-binding moiety, heterocyclic moieties with 1-3 heteroatoms for selectivity, and cycloalkyl groups with specific substituents for pharmacokinetic optimization, thereby achieving high target engagement with controlled complexity through modular design
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
The novel KHK inhibitors effectively regulate fructose metabolism, minimizing tissue asymmetry and toxicity, thereby mitigating metabolic syndrome and associated comorbidities without adverse drug interactions.
Implementation Method 1
KHK catalyzes the ATP-dependent conversion of fructose to FIP
Data Source
AI summary
Compounds of formula:wherein the variable substituents are defined herein.