Discovery of Selective Transforming Growth Factor β Type II Receptor Inhibitors as Antifibrosis Agents.
Journal
ACS medicinal chemistry letters
ISSN: 1948-5875
Titre abrégé: ACS Med Chem Lett
Pays: United States
ID NLM: 101521073
Informations de publication
Date de publication:
13 May 2021
13 May 2021
Historique:
received:
30
12
2020
accepted:
19
04
2021
entrez:
31
5
2021
pubmed:
1
6
2021
medline:
1
6
2021
Statut:
epublish
Résumé
Historically, modulation of transforming growth factor β (TGF-β) signaling has been deemed a rational strategy to treat many disorders, though few successful examples have been reported to date. This difficulty could be partially attributed to the challenges of achieving good specificity over many closely related enzymes that are implicated in distinct phenotypes in organ development and in tissue homeostasis. Recently, fresolimumab and disitertide, two peptidic TGF-β blockers, demonstrated significant therapeutic effects toward human skin fibrosis. Therefore, the selective blockage of TGF-β signaling assures a viable treatment option for fibrotic skin disorders such as systemic sclerosis (SSc). In this report, we disclose selective TGF-β type II receptor (TGF-βRII) inhibitors that exhibited high functional selectivity in cell-based assays. The representative compound
Identifiants
pubmed: 34055221
doi: 10.1021/acsmedchemlett.0c00679
pmc: PMC8155245
doi:
Types de publication
Journal Article
Langues
eng
Pagination
745-751Informations de copyright
© 2021 American Chemical Society.
Déclaration de conflit d'intérêts
The authors declare no competing financial interest.
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