AHR Activator Compounds for Selective FOXA1-High Cancer Killing
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Identifying therapeutic compounds that can selectively kill neoplastic cells characterized by specific molecular traits, particularly those expressing high levels of the FOXA1 transcription factor and/or its gene targets, remains a challenge in oncology.
Innovation Solution
Utilizing CGS-15943, MRS-1220, SCH-58261, and their furan ring derivatives, which activate the aryl hydrocarbon receptor (AHR) to selectively target and kill FOXA1-high cancer cells, including breast, liver, and prostate cancers, particularly luminal and ER-positive breast cancers.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional chemotherapy agents are used, then cancer cells are killed, but selective killing of FOXA1-high cancer cells is not achieved
Solution Approach 1:
The patent applies local quality by designing compounds that selectively target and kill only FOXA1-high cancer cells while sparing other cell types. The compounds (CGS-15943, MRS-1220, SCH-58261 and their furan ring derivatives) exhibit enhanced cytotoxicity specifically in cancer cells with high FOXA1 expression, such as luminal and ER-positive breast cancers, liver cancers, and prostate cancers, thereby achieving selective killing based on the molecular trait of the target cells.
2Productivity
If compounds with high cytotoxicity are used, then cancer cell killing is enhanced, but off-target effects and toxicity may increase
Solution Approach 1:
The patent employs a discovery approach where compounds are identified and validated through high-throughput screening and functional assays, allowing rapid iteration and selection of the most effective candidates with minimal off-target effects. The furan ring-containing derivatives were specifically designed to enhance cytotoxicity while maintaining selectivity, effectively replacing less effective parent compounds through a systematic evaluation process.
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
These compounds demonstrate enhanced cytotoxicity in FOXA1-high cancer cells, providing a targeted therapeutic approach with potential for effective treatment and prevention of these cancers.
Implementation Method 1
These compounds exhibit enhanced killing of certain neoplasia cells—particularly neoplasia cells that express high levels of the FOXA1 transcription factor and/or gene targets of FOXA1—via a mechanism that appears to involve these compounds' herein described activation of the aryl hydrocarbon receptor (AHR)
Data Source
AI summary
The present disclosure relates to compositions and methods for the diagnosis and treatment or prevention of cancers, particularly cancers that exhibit elevated expression of FOXA1 and/or FOXA1 gene targets, such as certain breast, liver and/or prostate cancers, including luminal and/or ER-positive forms of breast cancer. Three previously identified adenosine receptor antagonists, CGS-15943, MRS-1220 and SCH-58261, as well as furan ring moiety-possessing derivatives of CGS-15943 are specifically provided for killing cancer cells in a manner that appears to involve activation of the aryl hydrocarbon receptor (AHR) by such compounds. The instant disclosure therefore provides for selecting and/or administering CGS-15943, MRS-1220, SCH-58261 and/or a furan-possessing derivative of CGS-15943, MRS-1220 and/or SCH-58261 as a therapeutic agent to target a cancer cell and/or subject having or at risk of developing a cancer. Methods and compositions for therapies that include such compounds are also provided.