Chromanone HLA-DR Inhibitors for Blocking Autoantigen Presentation
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Solution Overview
Problem
Current treatments for autoimmune diseases associated with HLA-DRB1, such as rheumatoid arthritis, ulcerative colitis, and multiple sclerosis, fail to effectively inhibit the presentation of autoantigens by HLA-DR, leading to unnecessary immune system attacks on the body's own tissues.
Innovation Solution
Development of chromanone compounds that act as inhibitors of antigen presentation by HLA-DR, blocking the interaction between HLA-DR/peptide complexes and T cells to prevent autoimmune responses.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current treatments for autoimmune diseases are used, then disease management is maintained, but they fail to effectively inhibit HLA-DR-mediated antigen presentation, leading to continued immune system attacks on body tissues
Solution Approach 1:
The patent introduces small molecule compounds as intermediary substances that bind to HLA-DR molecules, blocking the interaction between HLA-DR/peptide complexes and T cell receptors. These small molecules act as mediators that prevent the harmful immune recognition process without requiring genetic modification or complex biological agents, thereby reducing tissue destruction while maintaining disease management
Solution Approach 2:
The invention modifies the binding parameters of HLA-DR by introducing small molecule ligands that compete with peptide antigens for binding to the HLA-DR peptide-binding groove. This changes the binding affinity and specificity parameters of HLA-DR, preventing autoantigen presentation to T cells while maintaining the overall function of the MHC-II system
2Reliability
If HLA-DR/peptide complexes are presented to T cells, then immune response activation occurs, but autoantigens are erroneously recognized as foreign pathogens causing autoimmune disease
Solution Approach 1:
Small molecule compounds serve as intermediary blockers between HLA-DR/peptide complexes and T cell receptors. These molecules bind to HLA-DR and physically prevent the T cell receptor from accessing the peptide-binding groove, thereby eliminating erroneous autoantigen recognition while preserving the normal antigen presentation function of HLA-DR for non-autoimmune pathogens
Solution Approach 2:
Instead of trying to enhance T cell specificity to distinguish self from non-self antigens, the invention inverts the approach by blocking the HLA-DR presentation function for autoantigens specifically. This reverses the problem-solving strategy from improving immune discrimination to preventing harmful immune activation through competitive inhibition at the HLA-DR level
Data Source
AI summary
Chromanone compounds, pharmaceutical compositions containing them, methods of making them, and methods of using them including methods for treating disease states, disorders, and conditions associated with the inhibition of antigen presentation by HLA-DR.