Chalcone Estrogenic Compounds for Non-ER Signaling Without Agonism

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Solution Overview

Problem

Current estrogen therapies, such as menopausal hormone therapy (MHT), while effective for treating menopausal symptoms, increase the risk of adverse outcomes like breast and uterine cancer, stroke, and Alzheimer's disease due to their mixed agonist/antagonist activity on estrogen receptors.

Innovation Solution

Development of nuclear receptor reprogramming (NRRP) compounds that synergistically modulate estrogen receptor activity with estradiol, enhancing beneficial effects without agonist or antagonist activity, thereby reducing the risk of estrogen-related cancers.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If traditional estrogen therapies (MHT) are used to treat menopausal symptoms, then effectiveness in treating symptoms is improved, but risk of adverse outcomes (breast cancer, uterine cancer, stroke, Alzheimer's disease) increases

Engineering Contradiction:

Improveeffectiveness in treating menopausal symptomsVSAvoidrisk of adverse outcomes including cancers and stroke

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent extracts and eliminates the harmful agonist and antagonist activities from estrogen therapy by developing NRRP compounds that selectively modulate gene expression without activating or blocking estrogen receptors, thereby removing the cause of adverse outcomes while preserving beneficial effects

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The NRRP compounds act as intermediary molecules that indirectly influence estrogen signaling by modifying chromatin structure and gene accessibility, rather than directly binding to estrogen receptors, thus mediating the therapeutic effect without the harmful receptor interactions

Inventive Principle:

Principle #24Intermediary (Mediator)

2Reliability

If estrogen receptor agonist activity is enhanced to improve therapeutic effect, then treatment efficacy is improved, but risk of estrogen-related cancers increases

Engineering Contradiction:

Improvetreatment efficacyVSAvoidrisk of estrogen-related cancers

Core Design Contradiction:

ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent converts the harmful overactivation of estrogen receptors into a beneficial selective gene modulation approach, where NRRP compounds enhance beneficial estrogen-related gene expression while preventing activation of cancer-promoting genes, effectively transforming the mechanism from harmful to beneficial

Inventive Principle:

Principle #22Blessing in disguise (Convert harm into benefit)

Data Source

PatentUS20250228795A1Estrogenic compounds and methods of use

Publication Date: 2025.07.17 IATERION INC

AI summary

Estrogenic compounds and compositions, and a method, are presented. The novel estrogenic compounds comprise novel chalcone derivatives and analogs that have little or no measurable estrogen (estradiol, E2) activity but potentiate E2 activity without binding an estrogen receptor (ER). The novel compositions comprise one or more of the novel estrogenic compounds and may optionally comprise one or more excipients. The one or more excipients may be pharmaceutically acceptable. The one or more excipients may comprise at least one compound that does not occur in nature with estrogenic compounds. The method comprises administering a pharmaceutical composition comprising an estrogenic compound described herein to a patient in need of treatment with an estrogenic compound or pharmaceutical composition.