Cyclic Peptide Alpha4beta7 Integrin Antagonists
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
There is a need for improved α4β7 antagonists to effectively prevent or treat inflammatory and autoimmune diseases, as existing methods may not provide sufficient therapeutic benefits for conditions like Crohn's disease and ulcerative colitis.
Innovation Solution
Development of cyclic peptide compounds with specific structural formulas that inhibit α4β7 integrin, allowing for pharmaceutical compositions that can be administered orally, topically, or parenterally, exhibiting antagonistic activity against α4β7 integrin with selectivity over α4β1 integrin.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If monoclonal antibodies are used as α4β7 inhibitors, then therapeutic benefits are achieved for gastrointestinal diseases, but device complexity and manufacturing difficulty increase
Solution Approach 1:
The patent changes the molecular structure parameters from monoclonal antibodies to cyclic peptides with specific amino acid sequences and modifications (R1-R6 substituents), achieving simplified structure while maintaining therapeutic efficacy against α4β7 integrin for gastrointestinal diseases
Solution Approach 2:
The patent employs small molecular weight cyclic peptide compounds that can be orally administered, replacing complex monoclonal antibodies with simpler, more manufacturable peptide-based inhibitors that maintain therapeutic effectiveness
2Reliability
If conventional α4β7 antagonists are used, then inflammatory conditions are treated, but manufacturing precision and synthesis difficulty increase
Solution Approach 1:
The patent divides the peptide into modular components with defined amino acid sequences (Ile-Leu-Asp-Val core) and variable substituents (R1-R6), enabling systematic synthesis and precise control over molecular structure while maintaining antiinflammatory activity
Solution Approach 2:
The patent establishes specific structural parameters including cyclic peptide configuration, amino acid sequences, and substituent patterns that facilitate standardized synthesis procedures and improve manufacturing precision while preserving therapeutic activity
3Reliability
If peptide inhibitors are developed, then selectivity over α4β1 integrin is achieved, but loss of time in development increases
Solution Approach 1:
The patent performs preliminary structural optimization and selectivity testing during the design phase, establishing the cyclic peptide framework with specific amino acid sequences before clinical development, thereby reducing later-stage development time while maintaining selectivity over α4β1 integrin
Data Source
Figure 1
Figure 2
Figure 3
AI summary
There is described herein antagonists of α4β7 integrin, and more particularly to cyclic peptide antagonists. Accordingly, there is described herein a compound of formula (I) wherein R1, R2, R3, R4, R5, R6, R7 and R8 are various substituents; stereocentres 1*, 2* and 3* are each independently selected from R and S; n is 1, 2, 3, or 4 and where n is 2-4, Z is an amino terminus of an amino acid; -C=0- adjacent L is the carboxy terminus of an amino acid; and L along with Z and -C=0- is a peptide.