Modular c-MET PROTAC Degrader for Targeted Protein Elimination

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Solution Overview

Problem

Existing technologies lack effective methods to target and degrade specific proteins, such as cMET proteins, which are implicated in 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 Chemical Formula 1, to induce targeted protein degradation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If PROTAC compound is designed to bind to 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 distinct functional modules: (1) cMET binding moiety containing specific pharmacophores that recognize cMET protein, (2) E3 ligase binding moiety that recruits E3 ligase, and (3) linker that connects the two moieties. This segmentation allows each module to be independently optimized for its specific function while maintaining overall molecular functionality.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The linker serves as an intermediary element that mediates the interaction between the cMET binding moiety and the E3 ligase binding moiety. It provides the necessary spatial separation and orientation to enable simultaneous binding to both targets while maintaining structural flexibility for effective protein-protein interaction.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Adaptability or versatility

If novel cMET binding moiety and E3 ligase binding moiety are connected via linker, then new PROTAC compound is created, but synthesis difficulty increases

Engineering Contradiction:

ImprovePROTAC compound versatilityVSAvoidsynthesis ease

Core Design Contradiction:

Adaptability or versatilityVSEase of manufacture

Solution Approach 1:

The synthesis strategy segments the PROTAC molecule into separately synthesizable moieties that can be coupled through established chemical reactions. The cMET binding moiety and E3 ligase binding moiety are synthesized independently using standard organic synthesis techniques, then joined via linker attachment at specific functional groups.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The linker design incorporates universal coupling capabilities that can connect to various cMET binding moieties and E3 ligase binding moieties through standard chemical reactions. This universal interface approach allows the same linker structure to be used across different PROTAC variants, simplifying the overall synthesis process.

Inventive Principle:

Principle #6Universality (Multi-functionality)

Data Source

PatentEP4624472A1Degrader including novel c-met protein ligand and pharmaceutical composition including 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.