Optimization of small molecule degraders and antagonists for targeting estrogen receptor based on breast cancer: current status and future.
estrogen receptor
selective estrogen receptor covalent antagonist
selective estrogen receptor degrader
small molecule drugs
structural optimization
Journal
Frontiers in pharmacology
ISSN: 1663-9812
Titre abrégé: Front Pharmacol
Pays: Switzerland
ID NLM: 101548923
Informations de publication
Date de publication:
2023
2023
Historique:
received:
20
05
2023
accepted:
05
09
2023
medline:
9
10
2023
pubmed:
9
10
2023
entrez:
9
10
2023
Statut:
epublish
Résumé
The estrogen receptor (ER) is a classical receptor protein that plays a crucial role in mediating multiple signaling pathways in various target organs. It has been shown that ER-targeting therapies inhibit breast cancer cell proliferation, enhance neuronal protection, and promote osteoclast formation. Several drugs have been designed to specifically target ER in ER-positive (ER+) breast cancer, including selective estrogen receptor modulators (SERM) such as Tamoxifen. However, the emergence of drug resistance in ER+ breast cancer and the potential side effects on the endometrium which has high ER expression has posed significant challenges in clinical practice. Recently, novel ER-targeted drugs, namely, selective estrogen receptor degrader (SERD) and selective estrogen receptor covalent antagonist (SERCA) have shown promise in addressing these concerns. This paper provides a comprehensive review of the structural functions of ER and highlights recent advancements in SERD and SERCA-related small molecule drugs, especially focusing on their structural optimization strategies and future optimization directions. Additionally, the therapeutic potential and challenges of novel SERDs and SERCAs in breast cancer and other ER-related diseases have been discussed.
Identifiants
pubmed: 37808197
doi: 10.3389/fphar.2023.1225951
pii: 1225951
pmc: PMC10551544
doi:
Types de publication
Journal Article
Review
Langues
eng
Pagination
1225951Informations de copyright
Copyright © 2023 Yao, Tao, Hu, Li, Xue, Zhang and Lei.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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