cMET PROTAC Degrader With Modular Linker-Mediated Targeting

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Solution Overview

Problem

Existing technologies lack effective methods to target and degrade cMET proteins, which are associated with various diseases, particularly cancer, using PROTAC compounds.

Innovation Solution

A novel PROTAC compound is developed, comprising a cMET protein-binding moiety and an E3 ligase-binding moiety connected via a linker, represented by specific chemical formulas, to induce targeted protein degradation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If PROTAC compound is designed to bind cMET protein and E3 ligase simultaneously, then targeted protein degradation is achieved, but molecular complexity increases

Engineering Contradiction:

Improvetargeted protein degradation efficacyVSAvoidmolecular structure complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The PROTAC molecule is segmented into three functional modules: cMET binding moiety, E3 ligase binding moiety, and linker. This segmentation allows each component to perform its specific function independently while maintaining overall molecular functionality, resolving the complexity issue through modular design

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The linker serves as an intermediary component connecting the cMET binding moiety and E3 ligase binding moiety. This intermediary structure enables the two binding moieties to function simultaneously while maintaining appropriate spatial orientation, achieving targeted degradation without excessive molecular complexity

Inventive Principle:

Principle #24Intermediary (Mediator)

2Reliability

If PROTAC compound brings target protein close to E3 ligase, then polyubiquitination is triggered, but spatial arrangement requirements increase

Engineering Contradiction:

Improvepolyubiquitination inductionVSAvoidspatial arrangement constraints

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The linker is designed with flexible characteristics allowing dynamic spatial arrangement. This flexibility enables the PROTAC to adapt its conformation to bring cMET and E3 ligase into proximity for polyubiquitination induction, while not imposing rigid spatial constraints that would increase molecular complexity

Inventive Principle:

Principle #15Dynamics

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

The PROTAC compound effectively binds to and degrades cMET proteins, offering therapeutic potential for cMET-related diseases, particularly cancer, by leveraging the PROTAC principle of polyubiquitination and proteasome degradation.

Implementation Method 1

PROTAC binds to both proteins simultaneously, bringing the target protein very close to E3 ligase

Methodology Applied

Scientific EffectProtein-protein interaction:

Implementation Method 2

E3 ligase, which recognizes the target protein as a substrate and triggers polyubiquitination and subsequent proteasome degradation

Methodology Applied

Scientific EffectEnzymatic catalysis: Enzyme

Data Source

PatentEP4624466A1Degrader for decomposing CMET protein, and pharmaceutical composition comprising same

Publication Date: 2025.10.01 INNOCURE THERAPEUTICS INC

Figure 1

AI summary

A TPD compound is disclosed. The present invention relates to a novel PROTAC compound binding to a cMET protein and a pharmaceutical composition comprising the same. The present invention relates to a PROTAC compound that binds to a cMET protein, and since it can bind to a cMET protein and degrade it, it can be useful for the treatment or prevention of diseases related to cMET protein. The compound of the present invention has an excellent anticancer effect and can also induce the degradation of cMET proteins, which can show a therapeutic effect on cMET and related diseases.