Modified GIP/GLP-1 Dual Agonists for Fatty Liver Treatment
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Solution Overview
Problem
Existing GIP/GLP-1 dual receptor agonists for treating non-alcoholic fatty liver disease and non-alcoholic steatohepatitis are limited by dose-limiting gastrointestinal side effects such as nausea and diarrhea, which compromise patient compliance and treatment effectiveness.
Innovation Solution
Development of novel compounds with the structure of Formula I, including specific amino acids and functional groups, which act as GIP/GLP-1 dual agonists, potentially reducing gastrointestinal side effects while maintaining therapeutic efficacy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If GIP/GLP-1 dual receptor agonists are used to treat NAFLD and NASH, then therapeutic efficacy is improved, but gastrointestinal side effects (nausea, vomiting, diarrhea) worsen
Solution Approach 1:
The patent applies parameter changes by modifying the molecular structure of GIP/GLP-1 dual agonists through systematic variations in amino acid sequences, cyclic constraints, and side chain modifications. These structural parameter changes result in compounds with improved gastrointestinal tolerability while maintaining therapeutic efficacy for NAFLD and NASH treatment
Solution Approach 2:
The patent employs composite materials by creating hybrid peptide structures that combine GIP and GLP-1 agonist activities in single molecules. These composite compounds feature dual receptor activation capabilities with modified amino acid compositions, including non-natural amino acids and cyclic constraints, to achieve both therapeutic efficacy and reduced gastrointestinal side effects
2Reliability
If high doses of GIP/GLP-1 dual receptor agonists are administered, then treatment effectiveness is improved, but patient compliance worsens due to dose-limiting gastrointestinal adverse events
Solution Approach 1:
The patent modifies molecular parameters to achieve effective therapeutic doses with improved gastrointestinal tolerability. By changing the chemical structure parameters of the dual agonists, the invention enables administration of doses sufficient for treating NAFLD and NASH while reducing the gastrointestinal adverse events that currently limit patient compliance
3Reliability
If GIP/GLP-1 dual receptor agonists are used, then metabolic hormone activity is improved, but gastrointestinal tolerability worsens
Solution Approach 1:
The patent creates composite peptide structures that integrate both GIP and GLP-1 agonist functionalities into single molecules. These composite compounds maintain robust metabolic hormone activity for treating NAFLD and NASH while incorporating structural modifications that improve gastrointestinal tolerability
Solution Approach 2:
The patent applies local quality by making specific localized modifications to the peptide structure, such as modifying particular amino acid residues, adding cyclic constraints at specific positions, or attaching side chains to specific locations. These localized changes preserve metabolic hormone activity while improving gastrointestinal tolerability
Data Source
AI summary
Disclosed herein are small molecule GIP/GLP-1 dual receptor agonist compositions, pharmaceutical compositions, the use and preparation thereof.