FGF401, A First-In-Class Highly Selective and Potent FGFR4 Inhibitor for the Treatment of FGF19-Driven Hepatocellular Cancer.
Journal
Molecular cancer therapeutics
ISSN: 1538-8514
Titre abrégé: Mol Cancer Ther
Pays: United States
ID NLM: 101132535
Informations de publication
Date de publication:
12 2019
12 2019
Historique:
received:
16
12
2018
revised:
12
06
2019
accepted:
06
08
2019
pubmed:
15
8
2019
medline:
8
7
2020
entrez:
15
8
2019
Statut:
ppublish
Résumé
Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver and it is the third leading cause of cancer-related deaths worldwide. Recently, aberrant signaling through the FGF19/FGFR4 axis has been implicated in HCC. Here, we describe the development of FGF401, a highly potent and selective, first in class, reversible-covalent small-molecule inhibitor of the kinase activity of FGFR4. FGF401 is exquisitely selective for FGFR4 versus the other FGFR paralogues FGFR1, FGFR2, FGFR3, and all other kinases in the kinome. FGF401 has excellent drug-like properties showing a robust pharmacokinetic/pharmacodynamics/efficacy relationship, driven by a fraction of time above the phospho-FGFR4 IC
Identifiants
pubmed: 31409633
pii: 1535-7163.MCT-18-1291
doi: 10.1158/1535-7163.MCT-18-1291
doi:
Substances chimiques
FGF19 protein, human
0
Fibroblast Growth Factors
62031-54-3
FGFR4 protein, human
EC 2.7.10.1
Receptor, Fibroblast Growth Factor, Type 4
EC 2.7.10.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2194-2206Informations de copyright
©2019 American Association for Cancer Research.