ACMSD Inhibitor Compositions for NAD+ Biosynthesis Disorders
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Solution Overview
Problem
There is a need for new and improved inhibitors of aminocarboxymuconate semialdehyde decarboxylase (ACMSD) to increase NAD+ levels and modify disease pathophysiologies associated with defects in NAD+ biosynthesis, as reduced levels of NAD+ are linked to various health issues including type 2 diabetes, mitochondrial diseases, and liver and kidney disorders.
Innovation Solution
Development of compounds and their pharmaceutically acceptable forms, derivatives, and pharmaceutical compositions that inhibit ACMSD, including specific structural formulas and prodrugs, to enhance NAD+ levels and treat conditions such as muscle structure disorders, neuronal activation disorders, muscle fatigue, muscle mass disorders, metabolic diseases, cancer, vascular diseases, ocular vascular diseases, liver diseases, and renal diseases.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If ACMSD inhibition is used to increase NAD+ levels, then neuronal degeneration is protected against and muscle function is improved, but the complexity of drug development increases due to the need for selective inhibitors
Solution Approach 1:
The patent applies parameter changes by systematically varying structural parameters of the inhibitor molecules (substituents at different positions, ring structures, chain lengths) to optimize both NAD+ boosting efficacy and selectivity for ACMSD over other enzymes, thereby reducing development complexity while maintaining reliability
Solution Approach 2:
The patent segments the inhibitor molecule into distinct functional regions (core structure, substituent groups, stereochemical elements) that can be independently optimized, allowing systematic development of selective ACMSD inhibitors without requiring complete redesign of the entire molecular structure
2Adaptability or versatility
If ACMSD inhibitors are developed to treat multiple disease states, then the versatility of the treatment approach increases, but the manufacturing precision requirements increase
Solution Approach 1:
The patent achieves universality by designing ACMSD inhibitors with core structures and substituent patterns that can treat multiple disease states (neurodegenerative disorders, metabolic diseases, mitochondrial dysfunction, cancer) through a single mechanism of action, thereby reducing the need for disease-specific drug variations and simplifying manufacturing requirements
Solution Approach 2:
The patent uses parameter changes in the molecular structure (different substituents, stereochemistry, chain lengths) to fine-tune the inhibitor's properties for specific disease indications while maintaining the core ACMSD inhibition mechanism, allowing flexible adaptation without compromising manufacturing precision
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 compounds effectively increase intracellular NAD+ levels, protecting against neuronal degeneration, improving muscle function, and enhancing lifespan, while addressing a range of pathophysiological states including inflammation and fibrosis associated with mitochondrial dysfunction.
Implementation Method 1
inhibitors of aminocarboxymuconate semialdehyde decarboxylase (ACMSD)... ACMSD is a zinc-dependent amidohydrolase that participates in picolinic acid (PA), quinolinic acid (QA) and NAD+ homeostasis
Data Source
AI summary
Disclosed herein are inhibitors of aminocarboxymuconate semialdehyde decarboxylase (ACMSD), pharmaceutical compositions and methods for using these compounds to treat or prevent one or more ACMSD-related diseases such as, for example, muscle structure disorders, neuronal activation disorders, muscle fatigue disorders, muscle mass disorders, beta oxidation diseases, metabolic diseases, cancer, vascular diseases, ocular vascular diseases, muscular eye diseases, liver diseases, inflammatory diseases or renal diseases.