Hybrid Fumarate-CORMs for Rapid CO Release and HO-1 Activation
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Solution Overview
Problem
Current CO-releasing molecules (CO-RMs) fail to effectively activate the HO-1/CO pathway due to poor CO-release capabilities, limiting their therapeutic efficacy in inflammatory and cardiovascular diseases.
Innovation Solution
Development of hybrid fumarate-CO-releasing molecules (fumarate-CORMs) that rapidly liberate CO and activate the Nrf2/HO-1 pathway, offering a 'burst effect' or sustained release, depending on the compound type, to enhance therapeutic outcomes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional CO-releasing molecules (CO-RMs) are used, then CO release is achieved, but the CO-release capability is poor and therapeutic efficacy is limited
Solution Approach 1:
The patent combines fumarate moiety with CO-releasing molecule to create a hybrid compound that integrates the CO-release function with fumarate's biological activity, achieving both rapid CO release and effective HO-1 activation for improved therapeutic efficacy
Solution Approach 2:
The patent modifies the chemical structure by incorporating fumarate group with specific physical and chemical properties that enhance CO-release kinetics, transforming the release profile from poor/slow to rapid/burst effect
2Reliability
If Nrf2/HO-1 activators are used, then protective proteome is stimulated, but the effect is delayed due to time required to mount cellular stress response
Solution Approach 1:
The hybrid fumarate-CORM provides CO upfront to rapidly initiate protection, while simultaneously activating Nrf2/HO-1 pathway for sustained protective proteome expression, eliminating the delay period
Solution Approach 2:
The patent merges the immediate CO-release mechanism with the sustained Nrf2/HO-1 activation pathway into a single hybrid molecule, achieving both rapid and long-lasting protective effects
3Speed
If hybrid fumarate-CORMs with burst effect are used, then rapid CO release is achieved, but the release duration is short
Solution Approach 1:
The patent designs bi-CORM compounds that release CO in periodic or sustained manner over extended periods, complementing the burst effect compounds for different therapeutic scenarios requiring prolonged CO delivery
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
Fumarate-CORMs demonstrate improved therapeutic activities by rapidly releasing CO, activating Nrf2 and inducing HO-1 protein expression, providing effective tissue protection in diseases where these pathways are crucial, with compounds like A and B showing fast and sustained CO release respectively.
Implementation Method 1
hybrid molecules comprising a fumarate moiety and a CO-releasing molecule (CORM) are capable of rapidly liberating CO and activating the Nrf2/HO-1 pathway
Data Source
AI summary
The present invention relates to hybrid fumarate-CO-releasing molecules capable of increasing heme oxygenase-1 (HO-1) activity and HO-1 protein expression and simultaneously releasing CO, their synthesis and their use in therapeutic applications, in particular their use in the treatment of inflammatory or cardiovascular diseases.