Cell-Permeable Succinates for Mitochondrial ATP Production

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Solution Overview

Problem

Current treatments for mitochondrial diseases are limited, and there is a need for compounds that can enhance mitochondrial ATP production, improve cell permeability, and have low toxicity.

Innovation Solution

Development of novel cell-permeable succinates and their precursors, which can cross cellular membranes and release succinate in the cytosol, thereby enhancing mitochondrial ATP production.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Power

If succinate is used to enhance mitochondrial ATP production, then ATP production is improved, but cell permeability deteriorates because succinate cannot readily cross the cellular membrane

Engineering Contradiction:

ImproveATP productionVSAvoidcell permeability

Core Design Contradiction:

PowerVSEase of operation

Solution Approach 1:

The patent uses cell-permeable esters (methyl, ethyl, propyl esters) as intermediary compounds that can cross the cellular membrane. These esters serve as prodrugs that are converted intracellularly to release succinate, thereby solving the permeability problem while maintaining the ATP production benefit

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent modifies the chemical parameters of succinate by converting it to different ester forms (methyl, ethyl, propyl esters). This parameter change in molecular structure improves cell permeability while the esters are designed to be hydrolyzed intracellularly to release the active succinate form

Inventive Principle:

Principle #35Parameter changes

2Ease of operation

If succinate derivatives are developed to improve cell permeability, then cell permeability is improved, but toxicity may increase

Engineering Contradiction:

Improvecell permeabilityVSAvoidtoxicity

Core Design Contradiction:

Ease of operationVSObject-affected harmful factors

Solution Approach 1:

The patent employs simple ester groups (methyl, ethyl, propyl) as temporary, easily metabolized carriers. These short-living prodrug forms are designed to be rapidly hydrolyzed intracellularly, minimizing their residence time and potential toxicity while delivering the succinate payload

Inventive Principle:

Principle #27Cheap short-living objects (Disposable)

Solution Approach 2:

The patent converts the potential harm of improved cell permeability (which could lead to off-target effects and toxicity) into a benefit by using highly selective ester prodrugs that are specifically hydrolyzed by intracellular esterases, ensuring that succinate is released primarily where needed and reducing systemic toxicity

Inventive Principle:

Principle #22Blessing in disguise (Convert harm into benefit)

3Power

If conventional succinate compounds are used, then ATP production is enhanced, but plasma half-life is short due to poor stability

Engineering Contradiction:

ImproveATP productionVSAvoidplasma half-life

Core Design Contradiction:

PowerVSDuration of action of stationary object

Solution Approach 1:

The patent extracts the carboxylic acid groups from succinate and replaces them with ester groups (methyl, ethyl, propyl esters). This extraction of the acidic functional groups improves plasma stability and half-life, while the esters are designed to be cleaved intracellularly to release the active succinate for ATP production

Inventive Principle:

Principle #2Taking out (Extraction)

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 ATP production in mitochondria, improve energy supply to cells, and have improved properties such as better cell permeability, longer plasma half-life, reduced toxicity, and increased energy release.

Implementation Method 1

one of them being succinate. The provision of the novel cell permeable succinates is envisaged to allow passage over the cellular membrane

Methodology Applied

Scientific EffectPassive diffusion: Diffusion

Implementation Method 2

which in addition to being cell permeable and releasing succinate in the cytosol are also potentially able to provide additional energy to the organism by the hydrolytic products resulting from either chemical or enzymatic hydrolysis of the succinate derivatives

Methodology Applied

Scientific EffectHydrolysis: Hydrolysis

Implementation Method 3

The main part of ATP produced and utilized in the eukaryotic cell originates from mitochondrial oxidative phosphorylation, a process to which high-energy electrons are provided by the Kreb's cycle

Methodology Applied

Scientific EffectOxidative phosphorylation:

Data Source

PatentUS12310940B2Cell-permeable succinate compounds

Publication Date: 2025.05.27 ABLIVA AB

AI summary

The present invention provides novel cell-permeable succinates and cell permeable precursors of succinate aimed at increasing ATP-production in mitochondria. The main part of ATP produced and utilized in the eukaryotic cell originates from mitochondrial oxidative phosphorylation, a process to which high-energy electrons are provided by the Kreb's cycle. Not all Kreb's cycle intermediates are readily permeable to the cellular membrane, one of them being succinate. The provision of the novel cell permeable succinates is envisaged to allow passage over the cellular membrane and thus the cell permeable succinates can be used to enhance mitochondrial ATP-output.