Search research articles

ABOUT JoVE

Overview Leadership Blog JoVE Help Center

AUTHORS

Publishing Process Editorial Board Scope & Policies Peer Review FAQ Submit

LIBRARIANS

Testimonials Subscriptions Access Resources Library Advisory Board FAQ

RESEARCH

JoVE Journal Methods Collections JoVE Encyclopedia of Experiments Archive

EDUCATION

JoVE Core JoVE Business JoVE Science Education JoVE Lab Manual Faculty Resource Center Faculty Site

Terms & Conditions of Use

Related Concept Videos

Transducer Mechanism: Nuclear Receptors

Transducer Mechanism: Nuclear Receptors

Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by

Same author

A molecular stabiliser of an inhibitory eIF2B-eIF2(αP) complex activates the Integrated Stress Response.

Nature communications·2026

Same author

Impact of <sup>18</sup> FDG-avidity and immunosuppression on idiopathic and genetic cardiomyopathies.

medRxiv : the preprint server for health sciences·2026

Same author

Discovery and Optimization of Orally Bioavailable Heterobifunctional Degraders of KAT2A/B for the Treatment of Cancer.

Journal of medicinal chemistry·2026

Same author

Lessons from a National Liquid Biopsy Program to Provide Cancer Testing and Treatment for Patients with Advanced Solid Tumors.

Current oncology (Toronto, Ont.)·2026

Same author

Lessons learned in linking PROTACs from discovery to the clinic.

Nature reviews. Chemistry·2025

Same author

A Novel Small Molecule Allosteric Inhibitor of IL-17A from a DNA-Encoded Library.

ACS medicinal chemistry letters·2025

Search research articles

Related Experiment Video

Updated: Nov 9, 2025

Detecting the Ligand-binding Domain Dimerization Activity of Estrogen Receptor Alpha Using the Mammalian Two-Hybrid Assay

Detecting the Ligand-binding Domain Dimerization Activity of Estrogen Receptor Alpha Using the Mammalian Two-Hybrid Assay

Published on: December 19, 2018

Bispecific Estrogen Receptor α Degraders Incorporating Novel Binders Identified Using DNA-Encoded Chemical Library

Jeremy S Disch¹, Jennifer M Duffy¹, Esther C Y Lee¹

¹X-Chem Inc., 100 Beaver Street, Waltham, Massachusetts 02453, United States.

Journal of Medicinal Chemistry

|April 12, 2021

Summary

New Proteolysis Targeting Chimeras (PROTACs) offer a promising approach for ER+ breast cancer treatment. DNA-encoded chemical library screening identified novel ERα degraders, demonstrating efficacy in preclinical models.

More Related Videos

Screening for Phytoestrogens using a Cell-based Estrogen Receptor β Reporter Assay

Screening for Phytoestrogens using a Cell-based Estrogen Receptor β Reporter Assay

Published on: June 7, 2020

Detecting Estrogenic Ligands in Personal Care Products using a Yeast Estrogen Screen Optimized for the Undergraduate Teaching Laboratory

Detecting Estrogenic Ligands in Personal Care Products using a Yeast Estrogen Screen Optimized for the Undergraduate Teaching Laboratory

Published on: January 1, 2018

Related Experiment Videos

Last Updated: Nov 9, 2025

Detecting the Ligand-binding Domain Dimerization Activity of Estrogen Receptor Alpha Using the Mammalian Two-Hybrid Assay

Detecting the Ligand-binding Domain Dimerization Activity of Estrogen Receptor Alpha Using the Mammalian Two-Hybrid Assay

Published on: December 19, 2018

Screening for Phytoestrogens using a Cell-based Estrogen Receptor β Reporter Assay

Screening for Phytoestrogens using a Cell-based Estrogen Receptor β Reporter Assay

Published on: June 7, 2020

Detecting Estrogenic Ligands in Personal Care Products using a Yeast Estrogen Screen Optimized for the Undergraduate Teaching Laboratory

Detecting Estrogenic Ligands in Personal Care Products using a Yeast Estrogen Screen Optimized for the Undergraduate Teaching Laboratory

Published on: January 1, 2018

Area of Science:

Medicinal Chemistry
Molecular Biology
Oncology

Background:

Estrogen receptor alpha (ERα) signaling is a key driver in ER+ breast cancer.
Current ERα inhibitors like aromatase inhibitors, SERMs, and SERDs have limitations.
Novel therapeutic strategies targeting ERα are needed for improved breast cancer treatment.

Purpose of the Study:

To identify novel bispecific degraders of ERα using DNA-encoded chemical library (DECL) screening.
To evaluate the efficacy of these degraders in preclinical models of ER+ breast cancer.
To validate DECL screening as a method for discovering potent PROTACs.

Main Methods:

Screening of approximately 120 billion DNA-encoded molecules against ERα (wild-type and mutants).
Off-DNA synthesis and characterization of small molecule exemplars.
Rapid generation of bispecific degraders using click chemistry.
In vivo evaluation of PROTAC efficacy in a mouse xenograft model.

Main Results:

Identified exemplar 7 with nanomolar ERα binding, antagonism, and degradation.
Developed potent bispecific ERα degraders (PROTACs 18 and 21).
PROTACs 18 and 21 inhibited ER+ MCF7 tumor growth in vivo.
Demonstrated rapid generation of effective degraders with minimal optimization.

Conclusions:

DECL screening is an effective strategy for identifying novel ERα degraders.
Developed PROTACs show promise for treating ER+ breast cancer.
This approach facilitates the discovery of new therapeutic leads for cancer treatment.