AIF-CHCHD4 Interaction Assay for Cancer Compound Screening

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Solution Overview

Problem

Current cancer treatments lack effective methods to target mitochondrial activity in cancer cells, as the molecular mechanisms for therapeutic benefit remain undetermined, particularly in the interaction between AIF and CHCHD4 proteins.

Innovation Solution

A method is developed to identify compounds that inhibit the interaction between AIF and CHCHD4 proteins, using assays like ALPHA and SPR to assess their anticancer properties, facilitating high-throughput screening for potential cancer treatments.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If mitochondrial activity is targeted in cancer cells, then therapeutic benefit may be achieved, but the molecular mechanisms remain undetermined and lack of effective methods exists

Engineering Contradiction:

Improvetherapeutic benefitVSAvoidmolecular mechanisms

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The invention segments the complex mitochondrial import machinery into specific interactors (AIF and CHCHD4 proteins) that can be individually targeted. By focusing on the specific protein-protein interaction between AIF and CHCHD4 rather than the entire mitochondrial system, the complex molecular mechanism is broken down into manageable, targetable components while maintaining therapeutic reliability.

Inventive Principle:

Principle #1Segmentation

2Productivity

If high-throughput screening is implemented to identify compounds, then productivity increases, but measurement and assessment complexity increases

Engineering Contradiction:

Improvecompound identification speedVSAvoidinteraction assessment

Core Design Contradiction:

ProductivityVSDifficulty of detecting and measuring

Solution Approach 1:

The invention replaces complex biochemical interaction measurements with a luminescence-based detection system. The assay uses luminescent signals to report on AIF-CHCHD4 interaction status, substituting difficult-to-measure protein-protein interaction dynamics with a simple, high-throughput optical readout that can be rapidly automated across thousands of compounds.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

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

This method effectively identifies compounds that inhibit the AIF/CHCHD4 interaction, demonstrating anticancer properties and confirming their efficacy in cancer cell models, thereby offering a new approach to target mitochondrial activity in cancer cells.

Implementation Method 1

The measurement of the interaction between the AIF protein and the CHCHD4 protein can be carried out by means of an amplified luminescent proximity homogeneous assay (ALPHA)

Methodology Applied

Scientific EffectLuminescence: Luminescence

Implementation Method 2

The measurement of the interaction between the AIF protein and the CHCHD4 protein can be carried out by means of an amplified luminescent proximity homogeneous assay (ALPHA) or a surface plasmon resonance (SPR) assay

Methodology Applied

Scientific EffectSurface plasmon resonance:

Data Source

PatentUS20230221321A1Method for identifying compounds useful for the treatment of cancer

Publication Date: 2023.07.13 UNIV PARIS SACLAY

AI summary

The invention relates to a method for identifying compounds useful for the treatment of cancer based on assessing the ability of the compound to modulate the interaction between the AIF protein and the CHCHD4 protein.