Indolactam Dipeptides as Nanomolar Gli Inhibitors.
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:
14 Jul 2022
14 Jul 2022
Historique:
entrez:
21
7
2022
pubmed:
22
7
2022
medline:
22
7
2022
Statut:
epublish
Résumé
The Gli transcription factors within the Hedgehog (Hh) signaling pathway play essential roles in human development. However, the reactivation of Gli proteins in adult tissue is tumorigenic and drives the progression of several cancers, including the majority of basal cell carcinomas. Here we describe a novel set of indolactam dipeptides that target protein kinase C (PKC), exploiting the unique capacity of PKC isozymes to act as regulators of Gli. We devised an efficient synthetic route for the indolactam-based natural product (-)-pendolmycin and a series of analogues, and we evaluated these analogues in mechanistically distinct Gli reporter assays. The lead compound from these studies,
Identifiants
pubmed: 35859880
doi: 10.1021/acsmedchemlett.1c00562
pmc: PMC9290001
doi:
Types de publication
Journal Article
Langues
eng
Pagination
1036-1042Subventions
Organisme : NIGMS NIH HHS
ID : T32 GM007616
Pays : United States
Informations de copyright
© 2022 American Chemical Society.
Déclaration de conflit d'intérêts
The authors declare no competing financial interest.
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