CD38 Inhibitor Compounds for Raising Intracellular NAD+

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Solution Overview

Problem

Existing treatments fail to effectively increase NAD+ levels in cells, which are crucial for treating various diseases and disorders, particularly mitochondrial-related conditions.

Innovation Solution

Development of CD38 inhibitors, such as compounds represented by Formulas I, IIa, IIb, IIc, IIIa, IIIb, IIIc, IVa, IVb, and IVc, which inhibit the CD38 enzyme to raise NAD+ levels in cells.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If existing treatments are used, then disease management is attempted, but NAD+ levels in cells are not effectively increased

Engineering Contradiction:

ImproveNAD+ levelsVSAvoidtreatment effectiveness

Core Design Contradiction:

Quantity of substanceVSReliability

Solution Approach 1:

The patent extracts and targets the specific enzyme CD38, which is responsible for consuming NAD+ in cells. By developing inhibitors that specifically bind to and inhibit CD38 activity, the treatment removes the primary cause of NAD+ depletion, thereby effectively increasing intracellular NAD+ levels without affecting other cellular processes

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The patent changes the biochemical parameter of CD38 enzyme activity by introducing small molecule inhibitors that alter the enzyme's functional state. These compounds bind to CD38 and change its catalytic activity parameter, preventing NAD+ hydrolysis and thereby increasing NAD+ concentration in cells

Inventive Principle:

Principle #35Parameter changes

2Quantity of substance

If CD38 enzyme activity is not inhibited, then normal cellular metabolism is maintained, but NAD+ levels decrease leading to disease progression

Engineering Contradiction:

ImproveNAD+ levelsVSAvoiddisease conditions

Core Design Contradiction:

Quantity of substanceVSObject-generated harmful factors

Solution Approach 1:

The patent applies preliminary anti-action by preventing CD38-mediated NAD+ consumption before it can lead to pathological conditions. The inhibitors are designed to block CD38 activity in advance, maintaining adequate NAD+ levels prophylactically and preventing the development of NAD+-depletion-related diseases

Inventive Principle:

Principle #9Preliminary anti-action

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 increase intracellular NAD+ levels, providing therapeutic benefits for mitochondrial-related diseases and disorders, including non-alcoholic fatty liver disease, diabetes, obesity, and neurodegenerative conditions.

Implementation Method 1

CD38 inhibitors effectively increase intracellular NAD+ levels by inhibiting the CD38 enzyme

Methodology Applied

Scientific EffectEnzyme inhibition: Enzyme

Data Source

PatentUS12514858B2CD38 inhibitors

Publication Date: 2026.01.06 ASTELLAS ENGINEERED SMALL MOLECULES US INC

AI summary

One embodiment of the invention is a compound represented by Formula I: or a pharmaceutically acceptable salt thereof. The variables in Formula I are defined herein. Compounds of Formula I are CD38 inhibitors, which can be used to treat a disease or condition in a subject that benefits from an increase in NAD+ or to treat a mitochondrial disorder in a subject.