Development of HC-258, a Covalent Acrylamide TEAD Inhibitor That Reduces Gene Expression and Cell Migration.
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 Dec 2023
14 Dec 2023
Historique:
received:
06
09
2023
revised:
22
11
2023
accepted:
22
11
2023
pmc-release:
14
12
2024
medline:
20
12
2023
pubmed:
20
12
2023
entrez:
20
12
2023
Statut:
epublish
Résumé
The transcription factor YAP-TEAD is the downstream effector of the Hippo pathway which controls cell proliferation, apoptosis, tissue repair, and organ growth. Dysregulation of the Hippo pathway has been correlated with carcinogenic processes. A co-crystal structure of TEAD with its endogenous ligand palmitic acid (PA) as well as with flufenamic acid (FA) has been disclosed. Here we report the development of HC-258, which derives from FA and possesses an oxopentyl chain that mimics a molecule of PA as well as an acrylamide that reacts covalently with TEAD's cysteine. HC-258 reduces the
Identifiants
pubmed: 38116405
doi: 10.1021/acsmedchemlett.3c00386
pmc: PMC10726447
doi:
Types de publication
Journal Article
Langues
eng
Pagination
1746-1753Informations de copyright
© 2023 American Chemical Society.
Déclaration de conflit d'intérêts
The authors declare no competing financial interest.