EZH2 and SCD1 Inhibitor Combination for Solid Tumor Therapy

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Solution Overview

Problem

EZH2 inhibitors are ineffective in EZH2-overexpressing solid tumors, such as glioma and melanoma, due to simultaneous mutations in the Ras pathway and SWI/SNF, leading to poor therapeutic outcomes, and there is a need to enhance their anti-tumor efficacy.

Innovation Solution

A pharmaceutical composition combining an EZH2 inhibitor with an SCD1 inhibitor, where the mass ratio of EZH2 to SCD1 can vary from 10:10 to 10:1, is used to enhance the anti-tumor effect, specifically targeting breast cancer, melanoma, and other solid tumors.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If EZH2 inhibitor is used alone, then it can inhibit EZH2 activity in tumor cells, but it shows poor therapeutic effect in EZH2-overexpressing solid tumors due to simultaneous mutations in the Ras pathway and SWI/SNF

Engineering Contradiction:

Improvetherapeutic effectVSAvoidescape mechanism

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent combines EZH2 inhibitor with SCD1 inhibitor into a pharmaceutical composition for treating solid tumors. This combination approach addresses the limitation of EZH2 inhibitor monotherapy by simultaneously targeting both EZH2 and SCD1 pathways, preventing tumor cells from escaping through single-pathway mutations.

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The invention creates a composite pharmaceutical composition containing two different inhibitors (EZH2 inhibitor and SCD1 inhibitor) that work synergistically. This composite approach provides enhanced and more reliable therapeutic effect compared to single-agent therapy, as the dual mechanism of action overcomes the escape mechanisms present in EZH2-overexpressing solid tumors.

Inventive Principle:

Principle #40Composite materials

2Reliability

If EZH2 inhibitor is used, then it can regulate lipid metabolism in tumor cells, but the role of EZH2 in lipid metabolism regulation is not very clear and may lead to lipid accumulation

Engineering Contradiction:

Improveanti-tumor efficacyVSAvoidlipid accumulation

Core Design Contradiction:

ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent converts the harmful effect of lipid accumulation into a beneficial therapeutic outcome by combining EZH2 inhibitor with SCD1 inhibitor. While EZH2 inhibitor alone may cause lipid accumulation that could potentially harm the patient, the addition of SCD1 inhibitor targets this lipid metabolism pathway to prevent harmful accumulation while maintaining the anti-tumor efficacy.

Inventive Principle:

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

Solution Approach 2:

SCD1 inhibitor acts as an intermediary that mediates between EZH2 inhibitor therapy and lipid metabolism. It specifically targets the SCD1 enzyme involved in fatty acid synthesis, thereby regulating lipid metabolism and preventing harmful lipid accumulation that may result from EZH2 inhibition, while allowing the anti-tumor effects to proceed.

Inventive Principle:

Principle #24Intermediary (Mediator)

Data Source

PatentUS20240325385A1Anti-tumor pharmaceutical composition comprising EZH2 inhibitor and SCD1 inhibitor and use thereof

Publication Date: 2024.10.03 PEKING UNIVERSITY THIRD HOSPITAL (THE THIRD CLINICAL MEDICAL SCHOOL OF PEKING UNIVERSITY)

AI summary

Provided is a pharmaceutical composition for enhancing the anti-tumor effect of an EZH2 inhibitor. The pharmaceutical composition includes an EZH2 inhibitor and an SCD1 inhibitor. The SCD1 inhibitor enhances the effect of the EZH2 inhibitor on a solid tumor. Further provided are a related preparation of the pharmaceutical composition and the use thereof in the preparation of an anti-tumor drug.