Design, synthesis and biological evaluation of novel DCLK1 inhibitor containing purine skeleton for the treatment of pancreatic cancer.
Antitumor
DCLK1 inhibitor
Drug design
Pancreatic cancer
Journal
European journal of medicinal chemistry
ISSN: 1768-3254
Titre abrégé: Eur J Med Chem
Pays: France
ID NLM: 0420510
Informations de publication
Date de publication:
05 Dec 2023
05 Dec 2023
Historique:
received:
02
08
2023
revised:
27
09
2023
accepted:
28
09
2023
medline:
3
11
2023
pubmed:
21
10
2023
entrez:
20
10
2023
Statut:
ppublish
Résumé
Pancreatic cancer is a highly lethal form of malignancy that continues to pose a significant and unresolved health challenge. Doublecortin-like kinase 1 (DCLK1), a serine/threonine kinase, is found to be overexpressed in pancreatic cancer and holds promise as a potential therapeutic target for this disease. However, few potent inhibitors have been reported currently. Herein, a series of novel purine, pyrrolo [2,3-d]pyrimidine, and pyrazolo [3,4-d] pyrimidine derivatives were designed, synthesized, and evaluated their biological activities in vitro. Among them, compound I-5 stood out as the most potent compound with strong inhibitory activity against DCLK1 (IC
Identifiants
pubmed: 37862816
pii: S0223-5234(23)00813-9
doi: 10.1016/j.ejmech.2023.115846
pii:
doi:
Substances chimiques
Doublecortin-Like Kinases
EC 2.7.1.11
Intracellular Signaling Peptides and Proteins
0
Protein Serine-Threonine Kinases
EC 2.7.11.1
Pyrimidines
0
Purines
0
DCLK1 protein, human
EC 2.7.1.11
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
115846Informations de copyright
Copyright © 2023 Elsevier Masson SAS. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.