Hybrid STAC-NAD+ Compounds for Stability and Pharmacokinetics

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Solution Overview

Problem

Current SIRT1 activating compounds (STACs) face challenges due to low stability and inconsistent pharmacokinetics, limiting their effectiveness in boosting SIRT1 activity and alleviating age-related diseases as NAD+ levels decrease with age.

Innovation Solution

Development of hybrid compounds combining SIRT1 activating compounds (STACs) with NAD+ precursors, enhancing stability and pharmacokinetics, and increasing NAD+ levels to improve SIRT1 activation and bioavailability.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If NAD+ precursors are used to raise NAD+ levels, then SIRT1 activity is boosted, but stability and pharmacokinetics deteriorate

Engineering Contradiction:

ImproveSIRT1 activation effectivenessVSAvoidcompound stability

Core Design Contradiction:

ReliabilityVSStability of the object's composition

Solution Approach 1:

The patent combines STACs and NAD+ precursors into a single hybrid molecule structure. The STAC portion maintains SIRT1 binding capability while the NAD+ precursor portion provides stability and consistent pharmacokinetics, resolving the contradiction between effectiveness and stability

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The hybrid compound functions as a composite molecular structure integrating two distinct functional elements: the SIRT1-activating moiety and the NAD+ precursor moiety. This composite approach allows the molecule to simultaneously achieve reliable SIRT1 activation and improved stability/pharmacokinetics

Inventive Principle:

Principle #40Composite materials

2Reliability

If NAD+ precursors are used to raise NAD+ levels, then SIRT1 activity is boosted, but pharmacokinetics consistency deteriorates

Engineering Contradiction:

ImproveSIRT1 activation effectivenessVSAvoidpharmacokinetics consistency

Core Design Contradiction:

ReliabilityVSEase of operation

Solution Approach 1:

The hybrid compound merges the SIRT1-activating function with NAD+ precursor functionality into one molecule, ensuring that the compound delivers both SIRT1 activation and consistent pharmacokinetics as a unified therapeutic agent

Inventive Principle:

Principle #5Merging (Combining)

3Reliability

If STACs are used to activate SIRT1, then SIRT1 activity increases, but stability deteriorates

Engineering Contradiction:

ImproveSIRT1 activationVSAvoidcompound shelf life

Core Design Contradiction:

ReliabilityVSDuration of action of stationary object

Solution Approach 1:

The hybrid compound structure combines the SIRT1-activating STAC component with a stable NAD+ precursor component, creating a molecule that maintains both SIRT1 activation capability and extended stability/shelf life

Inventive Principle:

Principle #5Merging (Combining)

Data Source

PatentUS12252505B2SIRT1 activating compounds

Publication Date: 2025.03.18 PRESIDENT & FELLOWS OF HARVARD COLLEGE

AI summary

Provided herein are methods and compositions for preventing or treating aging, or an aging-related disorder, a disorder associated with inflammation, or for modulating an immune response in a subject in need thereof. In some embodiments, the methods comprise administering to the subject an effective amount of a compound of Formulas I-XIII.