YAP/TEAD Modulator Compounds for Target Gene Suppression

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

There is an unmet need for compounds that can modulate the interaction between YAP and TEAD proteins to treat diseases associated with the Hippo signaling pathway, particularly in cancers, as current YAP/TEAD inhibitors are not approved for human treatment.

Innovation Solution

Development of novel organic compounds, including pharmaceutically acceptable salts, tautomers, stereoisomers, and deuterated analogs, which can modulate the YAP/TEAD interaction, thereby reducing the expression of target genes and displaying anti-proliferative effects.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If existing YAP/TEAD inhibitors like Verteporfin are used, then the YAP/TEAD interaction is inhibited, but these compounds are not approved for human treatment and have limited therapeutic applicability

Engineering Contradiction:

Improvetherapeutic approval statusVSAvoidtherapeutic applicability

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent modifies the chemical structure of YAP/TEAD inhibitors by changing molecular parameters (Formula I with specific substituents R1-R6, rings A and B, and functional groups) to create compounds with improved pharmacological properties and therapeutic approval potential while maintaining YAP/TEAD inhibition activity

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent creates composite chemical structures combining multiple functional moieties in Formula I compounds that simultaneously target YAP/TEAD interaction while improving pharmacokinetic properties and therapeutic efficacy for human treatment applications

Inventive Principle:

Principle #40Composite materials

2Reliability

If novel compounds are developed to modulate YAP/TEAD interaction, then therapeutic efficacy is improved, but compound complexity and development requirements increase

Engineering Contradiction:

Improvetherapeutic efficacyVSAvoidcompound structure complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent divides the complex compound structure into manageable segments (Formula I with defined substituents R1-R6, rings A and B, and functional groups) that can be systematically designed and optimized to achieve YAP/TEAD modulation while controlling overall molecular complexity

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent creates a universal compound framework (Formula I) that can accommodate multiple substituents and functional groups to achieve various therapeutic effects through YAP/TEAD modulation, reducing the need for entirely separate compound designs for different indications

Inventive Principle:

Principle #6Universality (Multi-functionality)

Data Source

PatentUS20250376458A1Compounds and methods for YAP/TEAD modulation and indications therefor

Publication Date: 2025.12.11 OPNA BIO SA

AI summary

Disclosed are compounds of Formula (I):or a pharmaceutically acceptable salt, a tautomer, a stereoisomer, or a deuterated analog thereof, wherein ring A, ring B, Q, G, R2, R3, R4, R21, p, q, v, Y1, and Y2 are as described in any of the embodiments described in this disclosure; compositions thereof, and uses thereof.