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Updated: Dec 9, 2025

An In Vivo Estrogen Deficiency Mouse Model for Screening Exogenous Estrogen Treatments of Cardiovascular Dysfunction After Menopause
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The Quest for Orally Available Selective Estrogen Receptor Degraders (SERDs)

Lucia Wang1, Abhishek Sharma1

  • 1Department of Chemistry and Chemical Biology, Stevens Institute of Technology, Hoboken, New Jersey, 07030, USA.

Chemmedchem
|September 11, 2020
PubMed

Insights

New orally available selective estrogen receptor degraders (SERDs) show promise for treating resistant breast cancer. This review analyzes novel SERDs, focusing on their structure, binding, and pharmacokinetics for improved bioavailability.

Area of Science:

  • Endocrinology
  • Oncology
  • Medicinal Chemistry

Background:

  • Estrogen receptor-alpha (ERα) is a key target in ERα-positive breast cancer treatment.
  • Selective estrogen receptor degraders (SERDs) are crucial for resistant metastatic breast cancer.
  • Current SERDs like Fulvestrant have limited oral bioavailability.

Purpose of the Study:

  • To critically analyze recent advancements in orally available SERDs.
  • To focus on structure-activity relationships, binding interactions, and pharmacokinetics of novel SERDs.
  • To highlight promising SERDs developed from GW5638 analogues and other novel structures.

Main Methods:

  • Literature review of recent developments in orally available SERDs.
  • Analysis of structure-activity relationships (SAR) of novel SERD compounds.
  • Evaluation of binding interactions and pharmacokinetic properties of SERDs.

Main Results:

  • Several GW5638 analogues demonstrate promising oral bioavailability.
  • Structurally novel SERDs are emerging from pharmaceutical and academic research.
  • Ongoing clinical trials are evaluating some of these new SERDs.

Conclusions:

  • Orally available SERDs represent a significant advancement over injectable formulations.
  • Understanding SAR and pharmacokinetics is key to developing effective oral SERDs.
  • These novel agents hold potential for improved treatment of endocrine-resistant breast cancer.
Keywords:
anti-tumor agentscancerdrug designmedicinal chemistrystructure-activity relationships

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