Indole Compound Induces Regulatory T Cells

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Solution Overview

Problem

Current immunosuppressants for treating immune diseases like graft-versus-host disease and autoimmune disorders have limitations, including side effects and the challenge of obtaining sufficient numbers of regulatory T cells for therapeutic use.

Innovation Solution

The use of (tetrahydropyran-4-yl)-[2-phenyl-5-(1,1-dioxo-thiomorpholin-4-yl)methyl-1H-indol-7-yl]amine to induce differentiation and promote proliferation of regulatory T cells, forming a pharmaceutical composition that suppresses immune responses and treats immune diseases by activating these cells.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If high doses of cyclosporin A are used to completely suppress T cell activation, then immune response suppression is improved, but kidney toxicity and side effects worsen

Engineering Contradiction:
Improveimmune response suppressionVSAvoidkidney toxicity
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent uses a novel indole compound with a specific molecular structure (formula 1) that differs from conventional cyclosporin A in its chemical parameters. This structural parameter change enables the compound to suppress immune responses effectively while reducing kidney toxicity, as demonstrated in animal models where it showed comparable or superior efficacy to cyclosporin A with fewer side effects

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent creates a copy or analog of cyclosporin A's immunosuppressive function using a structurally similar but chemically distinct indole compound. This copy maintains the therapeutic effect of suppressing T cell activation and immune responses while improving the safety profile by reducing nephrotoxicity associated with the original cyclosporin A

Inventive Principle:
Principle #26Copying

2Object-affected harmful factors

If low doses of cyclosporin A are used to reduce side effects, then kidney toxicity is reduced, but medicinal effect decreases

Engineering Contradiction:
Improvekidney toxicityVSAvoidmedicinal effect
Core Design Contradiction:
Object-affected harmful factorsVSReliability

Solution Approach 1:

The novel indole compound (formula 1) has optimized chemical parameters that allow it to achieve effective immunosuppression at lower doses compared to cyclosporin A. The compound's specific molecular structure enables it to bind to cyclophilin with high affinity and selectively inhibit IL-2 production, providing therapeutic efficacy while minimizing side effects

Inventive Principle:
Principle #35Parameter changes

3Reliability

If conventional immunosuppressants are used to treat immune diseases, then immune response suppression is achieved, but the mechanism of action and toxicity site overlap with other immunosuppressants

Engineering Contradiction:
Improveimmune response suppressionVSAvoidmechanism of action overlap
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent employs a compound with selective local action on specific immune pathways. The indole compound specifically targets IL-2 production and T cell activation mechanisms, differentiating it from other immunosuppressants that may have broader or overlapping mechanisms. This selective local quality allows for combination therapy with other immunosuppressants having different toxicity profiles

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The compound acts as an intermediary substance that binds to cyclophilin (a cellular protein) to inhibit IL-2 production. This intermediary mechanism is distinct from other immunosuppressants that may directly inhibit T cell receptors or other pathways, providing a unique mechanism of action that can be combined with other agents having different mechanisms

Inventive Principle:
Principle #24Intermediary (Mediator)

Data Source

PatentEP2992881B1Pharmaceutical composition for inhibiting immune response through inducing differentiation into regulator t cells and promoting proliferation of regulator t cells
Publication Date: 2019.05.22 LG CHEM LTD
  • EP2992881B1 patent drawingFigure 1
  • EP2992881B1 patent drawingFigure 2(A)~2(C)
  • EP2992881B1 patent drawingFigure 3

AI summary

The present invention relates to new medical use of (tetrahydropyran-4-yl)-[2-phenyl-5-(1,1-dioxo-thiomorpholine-4-yl)methyl-1H-indol-7-yl]amine, and more particularly, to a pharmaceutical composition containing the compound as an active ingredient, which is used for inhibiting an immune response, and/or for inducing differentiation into regulator T cells from undifferentiated T cells and/or promoting proliferation of regulator T cells.