Chromanone HLA-DR Modulators for Blocking Autoantigen Presentation
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Solution Overview
Problem
Existing treatments fail to effectively inhibit antigen presentation by HLA-DR, leading to autoimmune diseases such as rheumatoid arthritis and Type 1 diabetes, by erroneously presenting autoantigens and triggering immune responses against the body's own tissues.
Innovation Solution
Development of chromanone compounds and pharmaceutical compositions that inhibit antigen presentation by HLA-DR, blocking the interaction between HLA-DR and T cells to prevent autoantigen recognition.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If HLA-DR presents autoantigens to T cells, then immune response is triggered, but self-tissues are destroyed
Solution Approach 1:
The patent introduces small molecule compounds as intermediaries that bind to HLA-DR molecules, preventing direct interaction between autoantigens and T cell receptors. These compounds act as mediators that block the harmful antigen presentation pathway while allowing HLA-DR to remain functional for presenting exogenous antigens.
Solution Approach 2:
The invention applies preliminary anti-action by designing compounds that preemptively block HLA-DR binding sites before autoantigens can interact with T cells. The compounds are administered to prevent the formation of harmful immune complexes rather than treating tissue damage after it occurs.
2Object-affected harmful factors
If small molecules block HLA-DR binding, then autoantigen recognition is prevented, but antigen presentation function may be inhibited
Solution Approach 1:
The patent applies local quality by designing compounds that specifically target the peptide-binding groove of HLA-DR where autoantigens bind, while leaving other functional regions of the molecule intact. This allows selective blockade of harmful autoantigen presentation while preserving normal antigen presentation functions.
Solution Approach 2:
The invention uses partial action by developing compounds that occupy only the critical binding interface between HLA-DR and autoantigens, rather than completely inactivating the HLA-DR molecule. This partial blockade is sufficient to prevent autoantigen recognition while maintaining overall antigen presentation capacity.
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.