Estrogen Receptor Covalent Antagonists: The Best Is Yet to Come.
Journal
Cancer research
ISSN: 1538-7445
Titre abrégé: Cancer Res
Pays: United States
ID NLM: 2984705R
Informations de publication
Date de publication:
15 04 2019
15 04 2019
Historique:
received:
27
11
2018
revised:
24
01
2019
accepted:
06
02
2019
pubmed:
7
4
2019
medline:
22
1
2020
entrez:
7
4
2019
Statut:
ppublish
Résumé
The development of tamoxifen and subsequent estrogen receptor alpha (ERα) antagonists represents a tremendous therapeutic breakthrough in the treatment of breast cancer. Despite the ability of ERα antagonists to increase survival rates, resistance to these therapies is an all-too-common occurrence. The majority of resistant tumors, including those with hotspot mutations in the ligand-binding domain of ERα, remain dependent on ERα signaling, indicating that either a more potent or novel class of antagonist could have clinical benefit. With this thought in mind, we developed a novel ERα antagonist that exhibits enhanced potency due to its ability to covalently target a unique cysteine in ER. This review describes the design of this antagonist, H3B-5942, and discusses opportunities for future improvements, which could reduce the risk of escape mutations to this therapeutic modality.
Identifiants
pubmed: 30952631
pii: 0008-5472.CAN-18-3634
doi: 10.1158/0008-5472.CAN-18-3634
doi:
Substances chimiques
Estrogen Receptor Antagonists
0
H3B-5942
0
Indazoles
0
Receptors, Estrogen
0
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
1740-1745Informations de copyright
©2019 American Association for Cancer Research.