AhR Modulators Block Immune Evasion
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Solution Overview
Problem
Current therapies fail to effectively address immune evasion mechanisms employed by tumor cells, particularly through the aryl hydrocarbon receptor (AhR) pathway, leading to suppressed anti-tumor immune responses and a need for improved compositions and methods for immunological modulation in autoimmune and inflammatory diseases.
Innovation Solution
Development of small molecule compounds and compositions that modulate AhR activity, represented by specific chemical formulas, to treat and prevent diseases associated with AhR, including cancers and inflammatory conditions, by enhancing immune responses and overcoming immune tolerance.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Object-affected harmful factors
If tumor cells release high concentrations of kynurenine and other AhR ligands in the tumor microenvironment, then AhR is activated resulting in suppression of APCs, Th and Tc, but this mechanism enables tumor cells to evade anti-tumor immune responses
Solution Approach 1:
The patent converts the harmful AhR activation by tumor cells into a beneficial therapeutic opportunity by using AhR antagonists to block this pathway. The antagonists prevent tumor-derived ligands from activating AhR, thereby reversing the immune suppression and restoring anti-tumor immunity. This transforms the tumor's evasion mechanism into a target for therapeutic intervention.
Solution Approach 2:
The patent introduces AhR antagonists as intermediary substances that mediate between the tumor microenvironment and the immune system. These antagonists bind to AhR, preventing ligand-induced activation and blocking the suppressive signaling pathway. This intermediary action restores the balance and enables effective anti-tumor immune responses.
2Reliability
If AhR agonists are used to treat autoimmune and inflammatory diseases, then immune responses are modulated beneficially, but the patent indicates a need for improved compositions and methods
Solution Approach 1:
The patent applies parameter changes by developing novel AhR modulator compounds with optimized chemical structures and pharmacological properties. The invention explores different chemical classes, binding affinities, and selectivity parameters to create improved therapeutics that enhance immune modulation while addressing challenges in composition development and manufacturing.
Data Source
AI summary
Provided herein are compounds, compositions and methods of using the compounds and compositions for the treatment of diseases modulated, as least in part, by AhR. The compounds are represented by formulae:wherein the letters and symbols X1, X2, Z, R1b, R1c, R1d, R1e, R2a, R2b, R2c and R2d have the meanings provided in the specification.