Ant-ligand Small Molecules for Cancer Apoptosis Induction

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Solution Overview

Problem

Current therapeutic approaches targeting the ADP/ATP translocator ANT for cancer treatment face challenges due to difficulties in cell penetration and specificity, as peptides used previously were not effective in inducing apoptosis efficiently.

Innovation Solution

Development of small organic compounds with a substituted nitrogenous heterocycle structure that specifically target ANT, demonstrating good cell penetration and biodisponibility, and inducing apoptosis by interacting with ANT, thereby inhibiting tumour growth.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If peptides are used to target ANT, then specificity for ANT is improved, but cell penetration capability deteriorates

Engineering Contradiction:
Improvespecificity for ANTVSAvoidcell penetration capability
Core Design Contradiction:
ReliabilityVSEase of operation

Solution Approach 1:

The patent transforms the chemical structure from peptide-based to small organic molecule-based, fundamentally changing the molecular parameters (size, hydrophobicity, membrane permeability) to achieve both ANT specificity and cell penetration capability

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent introduces a substituted nitrogenous heterocycle as an intermediary structure that mediates between the requirement for ANT binding specificity and the need for cell membrane penetration, acting as a bridge between the two conflicting requirements

Inventive Principle:
Principle #24Intermediary (Mediator)

2Ease of operation

If small organic compounds are designed for ANT targeting, then cell penetration is improved, but selectivity for ANT may deteriorate

Engineering Contradiction:
Improvecell penetrationVSAvoidselectivity for ANT
Core Design Contradiction:
Ease of operationVSReliability

Solution Approach 1:

The patent applies local quality by introducing specific functional groups (substituted nitrogenous heterocycle with carboxylic acid or ester substituents) at specific positions of the core structure, creating localized binding regions that maintain ANT selectivity while the overall small molecule structure ensures cell penetration

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The patent employs structure-activity relationship optimization where the molecular structure is dynamically adjusted through varying substituents (R1, R2, R3 groups) to achieve the optimal balance between cell penetration and ANT binding selectivity

Inventive Principle:
Principle #15Dynamics

3Reliability

If peptide-based ANT targeting is used, then ANT binding is achieved, but therapeutic efficacy deteriorates due to inability to induce apoptosis efficiently

Engineering Contradiction:
ImproveANT bindingVSAvoidtherapeutic efficacy in inducing apoptosis
Core Design Contradiction:
ReliabilityVSProductivity

Solution Approach 1:

The patent creates a simplified copy of the peptide's binding function using small organic molecules that replicate the ANT binding capability without the structural limitations of peptides, thereby achieving both binding and therapeutic efficacy

Inventive Principle:
Principle #26Copying

Solution Approach 2:

The patent adopts small organic molecules that can be easily synthesized, administered, and metabolized, replacing complex peptides with simpler, more effective therapeutic agents that achieve their purpose and are cleared from the system

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

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 induce apoptosis in cancer cells by targeting ANT, showing selective toxicity towards tumour cells while minimizing harm to normal cells, with optimized structures achieving enhanced killing efficiency and selectivity.

Implementation Method 1

molecules useful for inducing apoptosis or similar cell death mechanisms

Methodology Applied
Scientific EffectApoptosis:

Data Source

PatentEP2334380B1Ant-ligands molecules and biological applications
Publication Date: 2021.09.01 MITOLOGICS
  • EP2334380B1 patent drawingFigure 1A~2C
  • EP2334380B1 patent drawingFigure 3~4B
  • EP2334380B1 patent drawingFigure 5A~6

AI summary

The invention relates to molecules ANT-ligands having a substituted nitrogeneous heterocycle A wherein - A is a substituted pyrazinone of formula I, or - A is a substituted pyrazine of formula II, or A is a substituted pyridine group of formula III.