CXCR4 Antagonists for Stem Cell Mobilization

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Solution Overview

Problem

Current treatments for conditions such as cancer, HIV/AIDS, and stem cell mobilization are limited by the inefficiencies of G-CSF treatment, which only achieves successful stem cell mobilization in approximately 50% of cases, and do not effectively address neuropathic pain and inflammation associated with HIV and cancer metastasis.

Innovation Solution

Development of CXCR4 antagonists, specifically compounds that inhibit the CXCR4 receptor, to enhance stem cell mobilization, reduce HIV infectivity, and treat conditions like cancer metastasis, neuropathy, and inflammation by blocking the CXCR4-SDF-1 axis.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If G-CSF treatment is used for stem cell mobilization, then stem cells can be mobilized from bone marrow, but the success rate is only approximately 50% and treatment duration is extended to 4-5 days

Engineering Contradiction:

Improvestem cell mobilization success rateVSAvoidtreatment duration

Core Design Contradiction:

ReliabilityVSLoss of time

Solution Approach 1:

The patent changes the pharmacological parameter by introducing CXCR4 antagonists (a different mechanism of action) instead of continuing with G-CSF treatment. This parameter change achieves superior stem cell mobilization with higher success rates and shorter treatment duration, resolving the contradiction between reliability and time loss.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent uses CXCR4 antagonists as an intermediary substance that blocks the CXCR4-SDF-1 axis, thereby facilitating stem cell mobilization. This intermediary mechanism achieves more reliable and faster mobilization compared to direct G-CSF stimulation, resolving the technical contradiction.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Productivity

If G-CSF treatment is used for stem cell mobilization, then stem cells are released into circulation, but the expression of CXCR4 receptor is reduced which may affect re-engraftment efficiency

Engineering Contradiction:

Improvestem cell release efficiencyVSAvoidre-engraftment efficiency

Core Design Contradiction:

ProductivityVSReliability

Solution Approach 1:

The patent employs CXCR4 antagonists as intermediaries that block the CXCR4-SDF-1 interaction without altering CXCR4 receptor expression levels on stem cells. This allows efficient stem cell mobilization while preserving receptor integrity for optimal re-engraftment, resolving the contradiction between productivity and reliability.

Inventive Principle:

Principle #24Intermediary (Mediator)

3Productivity

If CXCR4 antagonists are used to block the CXCR4-SDF-1 axis, then stem cell mobilization efficiency is significantly improved, but the mechanism of action differs from conventional G-CSF treatment

Engineering Contradiction:

Improvestem cell mobilization efficiencyVSAvoidtreatment mechanism complexity

Core Design Contradiction:

ProductivityVSDevice complexity

Solution Approach 1:

The patent changes the fundamental parameter of treatment mechanism from G-CSF receptor stimulation to CXCR4 antagonist binding. This parameter change achieves superior mobilization efficiency through a different biological pathway, accepting increased mechanism complexity as a trade-off for significantly improved productivity.

Inventive Principle:

Principle #35Parameter changes

4Object-affected harmful factors

If CXCR4 antagonists are used for treating cancer metastasis, then the progression of cancer cells is inhibited, but the treatment must address multiple disease conditions simultaneously

Engineering Contradiction:

Improvecancer metastasis progressionVSAvoidtreatment applicability across multiple conditions

Core Design Contradiction:

Object-affected harmful factorsVSAdaptability or versatility

Solution Approach 1:

The patent applies the universal principle by using CXCR4 antagonists for multiple therapeutic indications including cancer metastasis, HIV/AIDS, neuropathy, and inflammatory conditions. This multi-functional approach allows a single mechanism to address diverse diseases, resolving the contradiction between targeting harmful factors and maintaining treatment versatility.

Inventive Principle:

Principle #6Universality (Multi-functionality)

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

CXCR4 antagonists significantly improve stem cell mobilization efficiency, reduce HIV infectivity, and provide therapeutic benefits for cancer, neuropathy, and inflammation by effectively blocking the CXCR4-SDF-1 axis, offering additive effects with other anti-angiogenic agents.

Implementation Method 1

CXCR4 antagonists significantly improve stem cell mobilization efficiency by effectively blocking the CXCR4-SDF-1 axis

Methodology Applied

Scientific EffectReceptor antagonism:

Implementation Method 2

reduce HIV infectivity by effectively blocking the CXCR4-SDF-1 axis

Methodology Applied

Scientific EffectReceptor antagonism:

Implementation Method 3

treat conditions like cancer metastasis, neuropathy, and inflammation by blocking the CXCR4-SDF-1 axis

Methodology Applied

Scientific EffectReceptor antagonism:

Implementation Method 4

treat conditions like cancer metastasis, neuropathy, and inflammation by blocking the CXCR4-SDF-1 axis

Methodology Applied

Scientific EffectReceptor antagonism:

Data Source

PatentEP2927224B8Receptor antagonists

Publication Date: 2018.12.19 PROXIMAGEN LLC

AI summary

The compounds of formula (I) are antagonists of the CXCR4 receptor Wherein R1, X, Y and R2 are as defined in the claims.