Copper Therapeutic Complexes for Stable CNS Delivery
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Solution Overview
Problem
Current therapeutics for neurological diseases like ALS and copper deficiency-related disorders, such as CuATSM, face challenges including inefficient copper delivery to the CNS, rapid crystallization, undesirable side reactions, and slow efficacy due to high affinity for human serum albumin, leading to gastrointestinal distress and limited therapeutic effectiveness.
Innovation Solution
Development of novel copper-based therapeutic compounds with improved formulation characteristics, such as those satisfying Formula I, which exhibit reduced crystallization, less negative reduction potentials, and enhanced copper release to the CNS, addressing the limitations of CuATSM.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If CuATSM is used as a therapeutic agent, then copper delivery to the CNS is achieved, but rapid crystallization occurs leading to formulation instability
Solution Approach 1:
The patent modifies the chemical structure of CuATSM by changing parameters such as the diimine ligand substituents (e.g., introducing electron-withdrawing groups like nitro or trifluoromethyl groups) to alter the compound's reduction potential and crystallization behavior. These parameter changes maintain copper delivery capability while reducing rapid crystallization and improving formulation stability.
2Reliability
If CuATSM is used for treatment, then therapeutic effect is provided, but undesirable side reactions occur due to high affinity for human serum albumin
Solution Approach 1:
The patent introduces specific local modifications to the CuATSM molecule, such as adding electron-withdrawing groups at particular positions on the diimine ligand. These local quality changes reduce the compound's affinity for human serum albumin while preserving its ability to deliver copper to the CNS, thereby minimizing side reactions like gastrointestinal distress.
3Reliability
If CuATSM is administered, then copper is delivered to enzymes, but slow efficacy results due to high albumin binding
Solution Approach 1:
By modifying the reduction potential parameter of CuATSM through structural changes (e.g., introducing electron-withdrawing groups), the patent accelerates copper release kinetics. This parameter change reduces the time required for copper delivery to essential enzymes while maintaining effective therapeutic levels, thereby improving therapeutic speed without sacrificing delivery effectiveness.
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
The new compounds effectively deliver copper to the CNS, improving therapeutic efficacy by increasing copper availability to essential enzymes, reducing side effects, and facilitating oral delivery, thus providing a more effective treatment for neurological diseases.
Implementation Method 1
The new compounds effectively deliver copper to the CNS, improving therapeutic efficacy by increasing copper availability to essential enzymes
Implementation Method 2
exhibit reduced crystallization, less negative reduction potentials, and enhanced copper release to the CNS
Data Source
AI summary
Disclosed herein are compound embodiments that are useful for treating a variety of diseases, particularly neurological diseases, motor neuron diseases, copper deficiency-related diseases, and/or mitochondrial deficiencies. The compound embodiments described herein also can be used in PET methods. Also disclosed herein are embodiments of methods of making and using the compound embodiments, as well as pharmaceutical formulations comprising the disclosed compound embodiments.