ACKR3 Small-Molecule Modulators for Cardiovascular Therapy

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Current therapeutic strategies for cardiovascular diseases and platelet disorders mediated by ACKR3 lack effective small molecules with high potency, selectivity, and low toxicity, necessitating the development of compounds that can modulate ACKR3 to inhibit or regulate its activity.

Innovation Solution

Development of novel compounds, including those following general formulas (Ia) to (Ig), which are small molecules with specific structural features such as cyclyl, heterocyclyl, and substituents, designed to inhibit, regulate, or modulate ACKR3, thereby treating cardiovascular diseases and platelet disorders with improved potency and selectivity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If existing therapeutic strategies are used for ACKR3-mediated cardiovascular diseases and platelet disorders, then treatment approach is established, but effective small molecules with high potency and selectivity are lacking

Engineering Contradiction:

Improveeffectiveness of ACKR3 modulationVSAvoidavailability of small molecule compounds

Core Design Contradiction:

ReliabilityVSEase of manufacture

Solution Approach 1:

The patent systematically modifies molecular parameters (chemical structure, substituents, functional groups) of ACKR3 ligands to optimize potency and selectivity. By changing chemical parameters such as introducing specific cyclyl and heterocyclyl groups with particular substituents, the compounds achieve high efficacy while maintaining small molecule characteristics for drug development.

Inventive Principle:

Principle #35Parameter changes

2Reliability

If compounds with high ACKR3 modulation potency are developed, then treatment efficacy is improved, but toxicity may increase

Engineering Contradiction:

Improvepotency of ACKR3 modulationVSAvoidtoxicity to humans and mammals

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent introduces specific local structural features (cyclyl groups at particular positions, heterocyclyl substituents) that locally enhance ACKR3 binding affinity and modulation potency while maintaining overall molecular safety profile. The localized chemical modifications achieve high efficacy without proportionally increasing systemic toxicity.

Inventive Principle:

Principle #3Local quality

3Reliability

If selectivity toward ACKR3 is improved, then side effects are reduced, but compound complexity may increase

Engineering Contradiction:

Improveselectivity toward ACKR3VSAvoidstructural complexity of compounds

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent divides the molecular structure into distinct functional segments: a core scaffold and specific substituent groups (cyclyl, heterocyclyl, aryl groups). This segmentation allows independent optimization of each component for ACKR3 selectivity while keeping the overall structure manageable and synthesizable as a small molecule.

Inventive Principle:

Principle #1Segmentation

Data Source

PatentEP4620949A1ACKR3 modulators for cardiovascular or antiplatelet therapy

Publication Date: 2025.09.24 LUXEMBOURG INSTITUTE OF HEALTH (LIH)

Figure 1
Figure 2~3
Figure 4

AI summary

The present invention discloses a compound of any of the general formulas (la) to (Ig): pharmaceutical compositions comprising said compounds and their use in the treatment of diseases, especially a disease is mediated by ACKR3, preferably a cardiovascular disease or a platelet disorder. In addition, method for treating a disease in which mediation, such as inhibition, regulation and/or modulation, of ACKR3 is beneficial in a human or a warm-blooded or mammal animal in need of such treatment is disclosed.