GIP/GLP-1 Dual Agonist Peptides With Lower GI Side Effects

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Solution Overview

Problem

Current GIP/GLP-1 dual receptor agonists for treating non-alcoholic fatty liver disease (NAFLD) are limited by gastrointestinal adverse events, leading to dose restrictions and compromised patient compliance.

Innovation Solution

Development of non-macrocyclic functionalized peptides acting as GIP/GLP-1 dual receptor agonists with specific structural modifications, including various stereoisomers and pharmaceutically acceptable salts, to enhance therapeutic efficacy while minimizing gastrointestinal side effects.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If GIP/GLP-1 dual receptor agonists are used to treat NAFLD, then therapeutic efficacy is improved, but gastrointestinal adverse events increase

Engineering Contradiction:

Improvetherapeutic efficacyVSAvoidgastrointestinal adverse events

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies parameter changes by modifying the chemical structure of GIP/GLP-1 dual receptor agonists through various substitutions at positions R1, R2, R4, R5, R6, and Z1-Z2. These structural parameter changes aim to optimize the balance between therapeutic efficacy and gastrointestinal tolerability, allowing the drug to maintain effectiveness while reducing adverse events through precise molecular engineering

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent employs composite material principles by creating complex peptidomimetic structures that combine multiple functional groups and stereoisomers. The compounds integrate various chemical moieties (heteroaryl groups, substituted alkyl chains, and stereocenters) to achieve dual receptor agonism with improved side effect profiles, effectively creating a composite molecular structure that balances efficacy and tolerability

Inventive Principle:

Principle #40Composite materials

2Reliability

If high doses of GIP/GLP-1 dual receptor agonists are administered, then treatment effectiveness is improved, but patient compliance deteriorates

Engineering Contradiction:

Improvetreatment effectivenessVSAvoidpatient compliance

Core Design Contradiction:

ReliabilityVSEase of operation

Solution Approach 1:

The patent utilizes parameter changes by optimizing the dose-response relationship through structural modifications. By adjusting molecular parameters (substituents at R1, R2, and other positions), the invention aims to achieve effective therapeutic outcomes at lower doses, thereby improving patient compliance while maintaining treatment effectiveness

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent applies the blessing in disguise principle by converting the harmful gastrointestinal side effects into a design constraint that drives structural optimization. By using the adverse events as feedback to guide molecular modifications, the invention transforms a harmful outcome into a beneficial design direction, ultimately achieving better tolerability and patient compliance

Inventive Principle:

Principle #22Blessing in disguise (Convert harm into benefit)

Data Source

PatentUS12533391B2Compositions and methods for the treatment of metabolic and liver disorders

Publication Date: 2026.01.27 VIKING THERAPEUTICS INC

AI summary

Disclosed herein are small molecule GIP/GLP-1 dual receptor agonist compositions, pharmaceutical compositions, the use and preparation thereof.