Small Molecule CD38 Inhibitors for NAD+ Elevation
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Solution Overview
Problem
Current technologies lack effective methods to inhibit CD38 activity and increase NAD+ levels in cells, which are crucial for mimicking the health benefits of dieting and exercise, as well as retarding age-related diseases.
Innovation Solution
Development of small molecules capable of inhibiting CD38 activity at nanomolar or micromolar concentrations, leading to increased cellular NAD+ levels and activation of NAD+-dependent processes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If CD38 activity is not inhibited, then NAD+ levels remain low, but inhibiting CD38 requires development of new small molecule compounds which increases device complexity
Solution Approach 1:
The patent applies parameter changes by systematically varying molecular parameters including substituent types (halo, hydroxy, alkoxy, amino groups), ring structures (5- or 6-membered heteroaryl rings), and positional isomers to optimize CD38 inhibition while maintaining manageable molecular complexity. This allows achieving effective NAD+ level elevation through controlled modification of compound parameters rather than requiring highly complex structures.
2Reliability
If high concentrations of inhibitors are used, then CD38 activity is suppressed, but this may cause off-target effects and reduce reliability
Solution Approach 1:
The patent applies local quality by designing compounds with specific heteroaryl ring systems (containing N, O, or S atoms) at defined positions, along with specific substituent patterns (halo, hydroxy, alkoxy, amino groups at particular positions). This localized structural optimization enables selective binding to CD38's active site, achieving reliable and selective inhibition that suppresses CD38 activity while minimizing off-target effects through precise local molecular features rather than relying on high concentrations.
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 described compounds effectively inhibit CD38, resulting in elevated NAD+ levels, which imparts the benefits of diet and exercise, including improved metabolic health and protection against age-related diseases.
Implementation Method 1
the primary enzymatic activity of CD38 is the hydrolysis of NAD+, resulting in the production of NAM and ADPR
Implementation Method 2
Small molecule inhibitors of CD38 could impart the health benefits of caloric restriction and exercise
Data Source
AI summary
The invention provides methods and compositions for inhibiting CD38 activity, and methods of treating or preventing various disorders associated with CD38 activity.