CD38 Inhibitors Modulate NAD+ Levels for Metabolic Disease Treatment
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Solution Overview
Problem
Current methods lack effective solutions for modulating cellular NAD+ levels to treat various metabolic and disease-related conditions, particularly where CD38 enzyme overexpression or decreased NAD+ levels contribute to disease progression.
Innovation Solution
Development of compounds that inhibit the CD38 enzyme, thereby increasing NAD+ levels by blocking its consumption, which can be administered to treat conditions such as nonalcoholic steatohepatitis, chronic obstructive pulmonary disorder, and rheumatoid arthritis.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If CD38 enzyme activity is not inhibited, then NAD+ levels remain low due to continuous consumption, but inhibiting CD38 enzyme activity causes accumulation of NAD+ which may lead to metabolic imbalance
Solution Approach 1:
The patent applies parameter changes by developing compounds that specifically modulate CD38 enzyme activity to achieve optimal NAD+ levels. The compounds of Formula I are designed to inhibit CD38 at controlled levels, transforming the metabolic parameter from NAD+ depletion to balanced NAD+ accumulation, thereby treating metabolic disorders without causing harmful imbalance
Solution Approach 2:
The patent uses small molecule compounds as intermediaries to mediate between CD38 enzyme and NAD+ metabolism. These compounds act as selective inhibitors that bridge the gap between complete enzyme inhibition (which would cause imbalance) and no inhibition (which maintains low NAD+), providing controlled modulation of NAD+ levels for therapeutic benefit
2Reliability
If current therapeutic methods are used for metabolic diseases, then disease progression continues due to depleted NAD+ levels, but developing new CD38 inhibitor compounds increases complexity of treatment protocols
Solution Approach 1:
The patent achieves universality by developing CD38 inhibitor compounds with broad therapeutic applicability across multiple metabolic diseases including obesity, type 2 diabetes, and neurodegenerative disorders. A single compound class (Formula I) addresses the common underlying mechanism of NAD+ depletion across different diseases, simplifying treatment approaches while maintaining reliability across diverse conditions
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 CD38 inhibitors effectively elevate blood and tissue NAD+ levels, providing therapeutic benefits for diseases associated with energy metabolism, oxidative stress, and cellular homeostasis, thereby attenuating disease progression in treated conditions.
Implementation Method 1
CD38 is one such consumer of NAD+. Also known as ADP ribosyl cyclase, CD38 is a type II membrane-anchored enzyme. It efficiently catalyzes the breakdown of NAD+ to nicotinamide and ADPR
Implementation Method 2
inhibitors of CD38 enzyme activity also modulate NAD+ tissue levels and would be useful in treating various diseases where CD38 is over expressed or where cellular NAD+ levels are depressed
Data Source
AI summary
Compounds of Formula (I) and methods of treating diseases of metabolism by modulating cellular NAD+ levels through the inhibition of the CD38 enzyme, are disclosed. Formula (I).