Aripiprazole–RAF Inhibitor Composition for Apoptosis Enhancement

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Solution Overview

Problem

Existing RAF inhibitors show remarkable anticancer efficacy but face resistance due to intratumor heterogeneity, necessitating a co-treatment strategy to lower resistant cell populations, while BIM induction alone is insufficient to cause significant apoptosis due to binding by antiapoptotic proteins.

Innovation Solution

A pharmaceutical and health functional food composition incorporating aripiprazole as an active ingredient to enhance the anticancer effect of RAF inhibitors by inducing apoptosis through increased expression of NOXA and PUMA proteins and PARP cleavage, either alone or in combination with RAF inhibitors.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If RAF inhibitors are used to treat cancer, then anticancer efficacy is improved at early stage, but resistance occurs in almost all cancers

Engineering Contradiction:

Improveanticancer efficacyVSAvoidtreatment duration

Core Design Contradiction:

ReliabilityVSDuration of action of stationary object

Solution Approach 1:

The patent combines RAF inhibitors with BH3 mimetics or BH3-only protein-inducing drugs in a co-treatment strategy. This merging of two different drug mechanisms addresses the resistance problem by simultaneously targeting multiple pathways, preventing resistant cell populations from emerging while maintaining the initial anticancer efficacy of RAF inhibitors

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The invention creates a composite therapeutic approach by formulating combinations of RAF inhibitors with BH3 mimetics or BH3-only protein-inducing agents. This composite treatment strategy leverages the synergistic effects of different drug classes to overcome resistance and extend durable response duration in cancer patients

Inventive Principle:

Principle #40Composite materials

2Reliability

If BIM induction is achieved through ERK signal inhibition, then apoptosis is increased, but BIM is bound and inhibited by antiapoptotic proteins

Engineering Contradiction:

Improveapoptosis inductionVSAvoidantiapoptotic protein inhibition

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent introduces BH3 mimetics or BH3-only protein-inducing drugs as intermediaries that displace BIM from antiapoptotic proteins. These intermediaries compete for binding sites on BCL2 family proteins, freeing BIM to induce apoptosis while simultaneously providing an additional apoptotic push through the BH3 mimetic activity

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The invention converts the harmful effect of antiapoptotic proteins binding and inhibiting BIM into a benefit by using BH3 mimetics to exploit the same binding interface. The BH3 mimetics bind to antiapoptotic proteins with high affinity, displacing BIM and converting the protective antiapoptotic function into a pro-apoptotic effect that enhances cancer cell death

Inventive Principle:

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

Data Source

PatentUS20250312334A1Composition containing aripiprazole as active ingredient for enhancing anticancer effect of RAF inhibitor

Publication Date: 2025.10.09 KOREA INST OF RADIOLOGICAL & MEDICAL SCI

AI summary

The present invention pertains to a composition for enhancing the anticancer effect of the RAF inhibitor, wherein the composition can treat cancer by acting as an agent for enhancing the anticancer effect of the RAF inhibitor when used in combination therapy with aripiprazole, wherein administering an effective amount of aripiprazole according to the present invention in combination with the RAF inhibitor is highly effective in enhancing the anticancer effect of the RAF inhibitor, such as by inducing cancer cell death, and thus the composition can be advantageously used as an agent for enhancing the anticancer effect of the RAF inhibitor.