ROR gamma modulators for type 2 diabetes complications

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Solution Overview

Problem

Current treatments for type 2 diabetes, such as insulin administration, do not cure the disease and lead to significant complications, and there is a lack of definitive treatment options for managing the condition effectively.

Innovation Solution

Development of compounds based on a polyhydroxylated cholane skeleton that act as selective ROR gamma receptor modulators or ligands, influencing adipogenesis and insulin resistance pathways to prevent or treat type 2 diabetes.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If insulin administration is used to treat type 2 diabetes, then blood glucose control is improved, but the disease is not cured and complications still occur

Engineering Contradiction:
Improveblood glucose controlVSAvoiddisease complications
Core Design Contradiction:
ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent introduces ROR gamma receptor modulators as intermediary compounds that act upstream in the pathological pathway. These modulators target the nuclear receptor ROR gamma to regulate adipogenesis and improve insulin sensitivity, addressing the root cause of insulin resistance rather than just managing blood glucose levels as insulin administration does.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The invention employs preliminary action by modulating ROR gamma receptor activity before severe complications develop. By preventing excessive adipogenesis and maintaining insulin sensitivity through ROR gamma modulation, the treatment aims to prevent the progression to advanced diabetic complications rather than merely managing symptoms after they occur.

Inventive Principle:
Principle #10Preliminary action

2Adaptability or versatility

If ROR gamma receptor modulation is used to improve insulin sensitivity, then a new treatment mechanism is provided, but the efficacy needs to be demonstrated compared to existing treatments

Engineering Contradiction:
Improvetreatment mechanismVSAvoidtreatment efficacy
Core Design Contradiction:
Adaptability or versatilityVSReliability

Solution Approach 1:

The patent employs parameter changes by modifying the biochemical parameters of ROR gamma receptor activity. The modulators alter the receptor's functional state to prevent aberrant adipogenesis and improve insulin sensitivity, representing a fundamental change in the therapeutic parameter from insulin replacement to receptor modulation upstream in the metabolic pathway.

Inventive Principle:
Principle #35Parameter changes

Data Source

PatentEP2758060B1ROR gamma modulators for treating diabetes ii complications
Publication Date: 2017.11.29 ETH ZURICH
  • EP2758060B1 patent drawingFigure 1
  • EP2758060B1 patent drawingFigure 2
  • EP2758060B1 patent drawingFigure 3

AI summary

The present invention relates to compounds of formula I, or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention, suppression or amelioration of a disease mediated by the ROR gamma receptor in a subject in need thereof, in particular diabetes and diabetes- related disorders, specifically type II diabetes, methods of their production, as well as methods of treatment or prevention of such diseases.