SOC Channel Modulators for Autoimmune Treatment
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Solution Overview
Problem
Current treatments for inflammatory and autoimmune disorders do not effectively modulate store-operated calcium (SOC) channel activity, which is crucial for regulating cellular functions such as cell proliferation and cytokine release.
Innovation Solution
Development of compounds of specific formulas (I, IA, II, IIA, III, IIIA, IV, IVA, V, VA, VIA, VII, VIIA) that inhibit SOC channel activity, including calcium-release activated calcium (CRAC) channels, by interacting with proteins in the SOC channel complex, thereby modulating intracellular calcium levels.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current treatments for inflammatory and autoimmune disorders are used, then general anti-inflammatory effects are achieved, but effective modulation of store-operated calcium channel activity is not achieved
Solution Approach 1:
The patent applies parameter changes by developing compounds with specific molecular structures (Formulas I-VIIA) that target SOC channels. The compounds feature specific chemical parameters including pyridine-2-amine core structures with particular substituents (R1-R11 groups), linkage types (L1, L2), and structural variations (X, Y, Z positions) that enable selective binding to and modulation of SOC channel proteins, thereby achieving effective treatment of inflammatory and autoimmune disorders through targeted calcium channel modulation
2Object-generated harmful factors
If SOC channel activity is inhibited, then cytokine release is reduced and therapeutic benefits are provided, but intracellular calcium levels are modulated
Solution Approach 1:
The patent employs intermediary action through compounds that act as mediators between the SOC channel and calcium influx. These compounds (with specific pyridine-2-amine structures and substituents) bind to SOC channel proteins including STIM and Orai, serving as intermediary agents that block the channel pore or prevent channel activation, thereby reducing pathological calcium influx and subsequent cytokine release while maintaining physiological calcium signaling
Data Source
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Figure 3A~3B
AI summary
Described herein are compounds and pharmaceutical compositions containing such compounds, which modulate the activity of store- operated calcium (SOC) channels. Also described herein are methods of using such SOC channel modulators, alone and in combination with other compounds, for treating diseases or conditions that would benefit from inhibition of SOC channel activity.