Synthesis and biological evaluation of 2,5-diaryl-1,3,4-oxadiazole derivatives as novel Src homology 2 domain-containing protein tyrosine phosphatase 2 (SHP2) inhibitors.
Antineoplastic Agents
/ chemical synthesis
Cell Line, Tumor
Cell Proliferation
/ drug effects
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Enzyme Inhibitors
/ chemical synthesis
Humans
Molecular Dynamics Simulation
Molecular Structure
Oxadiazoles
/ chemical synthesis
Protein Tyrosine Phosphatase, Non-Receptor Type 11
/ antagonists & inhibitors
Structure-Activity Relationship
2,5-diphenyl-1,3,4-oxadiazole derivatives
Inhibitors
SHP2
Structure-activity relationships (SAR)
Journal
Bioorganic chemistry
ISSN: 1090-2120
Titre abrégé: Bioorg Chem
Pays: United States
ID NLM: 1303703
Informations de publication
Date de publication:
11 2021
11 2021
Historique:
received:
02
06
2021
revised:
16
08
2021
accepted:
20
09
2021
pubmed:
4
10
2021
medline:
5
1
2022
entrez:
3
10
2021
Statut:
ppublish
Résumé
The Src homology-2 domain containing-protein tyrosine phosphatase-2 (SHP2) is a convergent node for oncogenic cell-signaling cascades including the PD-L1/PD-1 pathway. As an oncoprotein as well as a potential immunomodulator, SHP2 has now emerged as an attractive target for novel anti-cancer agents. Although significant progress has been made in identifying chemotypes of SHP2 inhibitors, these specific compounds might not be clinically useful to inhibit frequently encountered mutated SHP2 variants. Consequently, it is highly desirable to develop chemically different SHP2 inhibitors sensitive to SHP2 mutants. This work developed a new type of SHP2 inhibitors with 2,5-diaryl-1,3,4-oxadiazole scaffold. The representative compound 6l exhibited SHP2 inhibitory activity with IC
Identifiants
pubmed: 34601294
pii: S0045-2068(21)00761-6
doi: 10.1016/j.bioorg.2021.105384
pii:
doi:
Substances chimiques
Antineoplastic Agents
0
Enzyme Inhibitors
0
Oxadiazoles
0
1,3,4-oxadiazole
20O2F20OUR
PTPN11 protein, human
EC 3.1.3.48
Protein Tyrosine Phosphatase, Non-Receptor Type 11
EC 3.1.3.48
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
105384Informations de copyright
Copyright © 2021 Elsevier Inc. All rights reserved.