CRAC Channel Modulators for Intracellular Calcium Control
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current methods fail to effectively modulate intracellular calcium levels and store-operated calcium channel activity, which are crucial for regulating various cellular functions and treating diseases such as inflammation and immune disorders.
Innovation Solution
The use of compounds that interact with STIM and Orai proteins to modulate intracellular calcium levels by inhibiting store-operated calcium entry, thereby reducing cytokine expression and secretion, and treating diseases by administering these compounds to mammals.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If store-operated calcium entry is activated to regulate cellular functions, then cellular responses to growth factors, neurotransmitters, and hormones are enhanced, but intracellular calcium levels become difficult to control and may lead to pathological conditions
Solution Approach 1:
The patent introduces STIM and Orai proteins as intermediary components that mediate between calcium store depletion and calcium influx. STIM proteins sense calcium levels in the endoplasmic reticulum and activate Orai channels in the plasma membrane, providing a controlled and regulated pathway for calcium entry rather than uncontrolled influx, thus maintaining reliability while improving controllability of intracellular calcium levels.
2Productivity
If calcium release-activated calcium channels are used for store-operated calcium influx, then refilling of intracellular calcium stores and activation of enzymatic activity are improved, but cytokine expression and secretion are excessively activated leading to inflammation and immune disorders
Solution Approach 1:
The patent modulates the activity parameters of CRAC channels by introducing STIM and Orai proteins that can be regulated by various factors including pharmacological agents. This allows precise control over calcium influx magnitude and duration, enabling sufficient calcium entry for store refilling and enzymatic activation while preventing excessive activation that would lead to pathological cytokine expression and inflammation.
3Reliability
If current methods are used to modulate intracellular calcium levels, then some cellular functions are regulated, but the methods fail to effectively control store-operated calcium channel activity and intracellular calcium levels
Solution Approach 1:
The patent implements a feedback mechanism where STIM proteins continuously monitor calcium levels in the endoplasmic reticulum and adjust Orai channel activity accordingly. When calcium stores are depleted, STIM activates Orai channels to allow calcium influx; when stores are refilled, STIM deactivates the channels. This negative feedback loop provides precise control over intracellular calcium levels, overcoming the imprecision of current methods.
Data Source
AI summary
Described herein are compositions and uses thereof related to Ca2+ release-activated Ca2+ (CRAC) channel activity. Also described herein CRAC channel modulators for treating diseases or conditions that would benefit from inhibition of SOC channel activity.