Optimization of the Lead Compound NVP-BHG712 as a Colorectal Cancer Inhibitor.
EPH receptors
colorectal cancer
drug discovery
medicinal chemistry
structural biology
Journal
Chemistry (Weinheim an der Bergstrasse, Germany)
ISSN: 1521-3765
Titre abrégé: Chemistry
Pays: Germany
ID NLM: 9513783
Informations de publication
Date de publication:
21 Apr 2023
21 Apr 2023
Historique:
received:
19
12
2022
pmc-release:
21
04
2024
medline:
28
4
2023
pubmed:
18
2
2023
entrez:
17
2
2023
Statut:
ppublish
Résumé
The ephrin type-A receptor 2 (EPHA2) kinase belongs to the largest family of receptor tyrosine kinases. There are several indications of an involvement of EPHA2 in the development of infectious diseases and cancer. Despite pharmacological potential, EPHA2 is an under-examined target protein. In this study, we synthesized a series of derivatives of the inhibitor NVP-BHG712 and triazine-based compounds. These compounds were evaluated to determine their potential as kinase inhibitors of EPHA2, including elucidation of their binding mode (X-ray crystallography), affinity (microscale thermophoresis), and selectivity (Kinobeads assay). Eight inhibitors showed affinities in the low-nanomolar regime (K
Identifiants
pubmed: 36799129
doi: 10.1002/chem.202203967
pmc: PMC10133194
mid: NIHMS1876330
doi:
Substances chimiques
NVP-BHG712
0
Pyrazoles
0
Pyrimidines
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e202203967Subventions
Organisme : Intramural NIH HHS
ID : ZIA SC010355
Pays : United States
Informations de copyright
© 2023 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.
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