Cyclohexenone Compound Inhibits Ras Processing in Leukemia

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Solution Overview

Problem

Current treatments for leukemia lack effective compounds that target the underlying mechanisms of the disease, particularly the Ras signaling pathway, leading to limited therapeutic options and potential side effects.

Innovation Solution

A pharmaceutical composition comprising a therapeutically effective amount of a cyclohexenone compound, specifically a farnesylated quinone derivative isolated from Antrodia camphorata, which inhibits farnesyltransferase activity, thereby blocking Ras processing and triggering antitumor activity through multiple signaling pathways, including ERK1/2 and AMPK.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If current leukemia treatments are used, then therapeutic options are limited, but side effects and complications increase

Engineering Contradiction:
Improvetherapeutic optionsVSAvoidside effects
Core Design Contradiction:
Adaptability or versatilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies parameter changes by modifying the chemical structure of cyclohexenone compounds through various substituents (R1-R7 groups) to optimize therapeutic efficacy against leukemia while reducing side effects. The structural variations allow tuning of the compound's interaction with farnesyltransferase and downstream signaling pathways.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The cyclohexenone compound acts as an intermediary agent that blocks farnesyltransferase activity, thereby preventing Ras processing and downstream oncogenic signaling. This intermediary mechanism provides a targeted approach to leukemia treatment, offering new therapeutic options with potentially reduced side effects compared to conventional treatments.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Reliability

If farnesyltransferase activity is inhibited, then Ras processing is blocked, but therapeutic efficacy against leukemia is enhanced

Engineering Contradiction:
Improvetherapeutic efficacyVSAvoidmechanism complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent extracts and targets the specific farnesyltransferase enzyme in the Ras signaling pathway as a therapeutic intervention point. By isolating this specific enzymatic step for inhibition, the treatment addresses the root cause of leukemia pathogenesis with a targeted mechanism, enhancing therapeutic efficacy while providing a clear molecular target.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The cyclohexenone compound performs preliminary action by blocking farnesyltransferase activity before Ras can be processed and activated. This pre-emptive inhibition prevents the downstream activation of oncogenic signaling pathways, effectively stopping the disease process at an early molecular stage.

Inventive Principle:
Principle #10Preliminary action

3Object-generated harmful factors

If cyclohexenone compounds are used, then Ras processing is inhibited, but apoptosis and autophagy are induced

Engineering Contradiction:
Improvecancer cell survivalVSAvoidsignaling pathway involvement
Core Design Contradiction:
Object-generated harmful factorsVSDevice complexity

Solution Approach 1:

The patent employs inversion by inducing apoptosis and autophagy - normally protective or neutral cellular processes - to eliminate cancer cells. By hijacking these physiological pathways through farnesyltransferase inhibition, the treatment converts normal cellular mechanisms into therapeutic weapons against leukemia, enhancing cancer cell death while utilizing the body's own cellular processes.

Inventive Principle:
Principle #13The other way round (Inversion)

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 cyclohexenone compound effectively inhibits Ras processing and induces apoptosis and autophagy in cancer cells, demonstrating potential as a therapeutic agent for treating or reducing the risk of leukemia with reduced side effects and complications.

Implementation Method 1

inhibits farnesyltransferase activity, thereby blocking Ras processing

Methodology Applied
Scientific EffectEnzyme inhibition: Enzyme

Data Source

PatentEP2958558B1Methods and compositions for treating leukemia
Publication Date: 2018.06.13 GOLDEN BIOTECHNOLOGY CORP(CN)
  • EP2958558B1 patent drawingFigure 1
  • EP2958558B1 patent drawingFigure 2A~2C
  • EP2958558B1 patent drawingFigure 3A~3C

AI summary

The present invention provides methods and compositions for treating leukemia by cyclohexenone compounds. Leukemia (leukaemia) is a type of cancer of the blood or bone marrow characterized by an abnormal increase of immature while blood cells called "blasts". Leukemia is a broad term covering a spectrum of diseases. In turn, it is part of the even broader group of diseases affecting the blood, bone marrow, and lymphoid system, which are all known as hematological neoplasms.