Effects of MTX-23, a Novel PROTAC of Androgen Receptor Splice Variant-7 and Androgen Receptor, on CRPC Resistant to Second-Line Antiandrogen Therapy.
Journal
Molecular cancer therapeutics
ISSN: 1538-8514
Titre abrégé: Mol Cancer Ther
Pays: United States
ID NLM: 101132535
Informations de publication
Date de publication:
03 2021
03 2021
Historique:
received:
17
05
2020
revised:
29
08
2020
accepted:
30
11
2020
pubmed:
6
12
2020
medline:
3
11
2021
entrez:
5
12
2020
Statut:
ppublish
Résumé
Although second-line antiandrogen therapy (SAT) is the standard of care in men with castration-resistant prostate cancer (CRPC), resistance inevitably occurs. One major proposed mechanism of resistance to SAT involves the emergence of androgen receptor (AR) splice variant-7, AR-V7. Recently, we developed MTX-23 using the principle of proteolysis targeting chimera (PROTAC) to target both AR-V7 and AR-full length (AR-FL). MTX-23 has been designed to simultaneously bind AR's DNA binding domain (DBD) and the Von Hippel-Lindau (VHL) E3 ubiquitin ligase. Immunoblots demonstrated that MTX-23's degradation concentration 50% (DC
Identifiants
pubmed: 33277442
pii: 1535-7163.MCT-20-0417
doi: 10.1158/1535-7163.MCT-20-0417
doi:
Substances chimiques
Androgen Antagonists
0
Protein Isoforms
0
Receptors, Androgen
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
490-499Subventions
Organisme : NCI NIH HHS
ID : P30 CA072720
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA226746
Pays : United States
Informations de copyright
©2020 American Association for Cancer Research.
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