YAP/TEAD Modulator Compounds for Hippo Pathway Tumor Control
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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, that can modulate the YAP/TEAD interaction, thereby reducing the expression of target genes and displaying anti-proliferative effects.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If Verteporfin is used to target the Hippo signaling pathway by associating with YAP and inhibiting binding to TEAD, then the YAP/TEAD interaction is modulated, but the compound is not approved for human treatment and lacks sufficient therapeutic efficacy
Solution Approach 1:
The patent modifies the chemical structure of Verteporfin by changing parameters such as substituting the methoxy group with halogen atoms (chlorine, fluorine, bromine) at specific positions on the aromatic rings, and modifying the ester groups. These parameter changes in the molecular structure aim to improve binding affinity to YAP, enhance therapeutic efficacy, and optimize pharmacokinetic properties for human treatment approval
Solution Approach 2:
The invention creates composite chemical structures by combining modified porphyrin core structures with various substituent groups (halogen atoms, ester groups, alkyl chains). These composite molecular structures integrate multiple functional elements to achieve both high YAP binding affinity and improved drug-like properties for clinical application
2Adaptability or versatility
If no YAP/TEAD inhibitors are currently approved for human treatment, then there is an unmet need for new compounds, but developing new compounds requires extensive research and validation
Solution Approach 1:
The patent performs preliminary structure-activity relationship studies and computational modeling to predict which structural modifications of Verteporfin will optimize YAP binding. This preliminary action identifies promising candidate compounds before extensive preclinical and clinical testing, thereby reducing overall development time while maintaining high probability of success
Solution Approach 2:
The invention creates analogs and derivatives of Verteporfin by copying its core porphyrin structure and systematically modifying specific functional groups. This copying approach allows rapid generation of multiple candidate compounds with slightly varied structures, enabling parallel testing and accelerating the identification of clinically viable inhibitors
Data Source
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, G, R2, R3, R4, R20, p, q, v, X, and Z are as described in any of the embodiments described in this disclosure; compositions thereof; and uses thereof.