ER-alpha36 Modulating Compounds for Cancer and Asthma Treatment
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current treatments for estrogen receptor-related diseases, such as breast cancer and asthma, lack effective methods to modulate the novel estrogen receptor variant ER-α36, which is involved in cell proliferation and signaling, leading to inadequate prevention and treatment options.
Innovation Solution
Development of compounds and pharmaceutical compositions that modulate the function of ER-α36, inducing cell death, inhibiting cell proliferation, and treating diseases related to abnormal cell proliferation and asthma, by targeting specific domains of ER-α36 with compounds of Formula (I) and their derivatives.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current treatments for estrogen receptor-related diseases are used, then general disease management is maintained, but effective modulation of ER-α36 is lacking leading to inadequate prevention and treatment options
Solution Approach 1:
The patent segments the estrogen receptor system by specifically targeting the ER-α36 variant, which lacks the N-terminal AF-1 domain and C-terminal AF-2 domain compared to full-length hER-α66. This segmentation allows selective modulation of ER-α36 function without affecting other estrogen receptor variants, thereby improving treatment effectiveness while maintaining adaptability to specific disease contexts involving ER-α36 overexpression.
Solution Approach 2:
The compounds disclosed in the patent exhibit local quality by selectively binding to and modulating ER-α36 receptors in specific tissues and cell types where this variant is overexpressed, such as certain breast cancer cells and asthmatic airway cells. This localized action enhances treatment effectiveness at the disease site while preserving the ability to adapt to different ER-α36 expressing conditions through selective pharmacology.
2Reliability
If compounds that induce cell death and inhibit cell proliferation are used, then cancer treatment effectiveness is improved, but selectivity for ER-α36 versus other estrogen receptors must be maintained
Solution Approach 1:
The patent employs segmentation by designing compounds that specifically target the unique structural features of ER-α36, particularly the truncated form lacking AF-1 and AF-2 domains. This selective targeting ensures that cell death induction and proliferation inhibition effects are confined to ER-α36 expressing cells, minimizing off-target effects on full-length hER-α66 and hER-β receptors that retain both activation domains.
Solution Approach 2:
The disclosed compounds act as selective intermediaries that mediate between the therapeutic goal of inducing cell death and inhibiting proliferation in ER-α36 positive cells, and the constraint of avoiding harmful effects on other estrogen receptor variants. The compounds achieve this by selectively binding to ER-α36's unique ligand-binding pocket formed by its truncated structure, thereby translating therapeutic intent into selective biological action.
3Adaptability or versatility
If selective targeting of ER-α36 is achieved, then novel therapeutic approaches are provided, but development of specific compounds and pharmaceutical compositions is required
Solution Approach 1:
The patent applies universality by developing a series of compounds with a common structural scaffold (Formula I) that can selectively target ER-α36 across multiple disease contexts including breast cancer and asthma. This multi-functional approach allows the same compound class to provide novel therapeutic approaches for different ER-α36 related conditions, reducing the need for complete de novo development for each application while maintaining ease of manufacture through shared synthetic pathways and formulation strategies.
Data Source
AI summary
Provided herein in certain embodiments are compounds, pharmaceutical compositions and methods for modulating the functions of estrogen receptor alpha 36, for preventing and/or treating diseases related to estrogen receptor alpha 36, for preventing and/or treating respiratory diseases such as asthma, for inducing cell death and/or inhibiting cell proliferation and for preventing and/or treating diseases involving abnormal cell proliferation such as cancers.