Artemisinin derivative FO-ARS-123 as a novel VEGFR2 inhibitor suppresses angiogenesis, cell migration, and invasion

Autoren

Xiaohua Lu
Mohamed Elbadawi
Sebastian Blatt
Mohamed EM Saeed
Xiaolin Xiao
Xiao Ma
Edmond Fleischer
Peer W Kämmerer
Thomas Efferth

DOI

10.1016/j.cbi.2022.110062

ISSN

0009-2797

Zeitschrift

Chemico-Biological Interactions

Sprache

en

Artikelnummer

110062

Paginierung

110062 - 110062

Datum der Veröffentlichung

2022

Status

Published

Herausgeber

Elsevier BV

Herausgeber URL

http://dx.doi.org/10.1016/j.cbi.2022.110062

Datum der Datenerfassung

2024

Titel

Artemisinin derivative FO-ARS-123 as a novel VEGFR2 inhibitor suppresses angiogenesis, cell migration, and invasion

Ausgabe der Zeitschrift

365

Data source: Crossref

Abstract

Anti-angiogenesis targeting vascular endothelial growth factor receptor 2 (VEGFR2) has been considered an important strategy for cancer therapy. VEGFR2 inhibitors targeting tumor angiogenic pathways have been widely used in clinical cancer treatment. However, inherent or acquired resistance to anti-angiogenic drugs may occur and thus limit their clinical application. New VEGFR2 inhibitors are still highly demanded. The aim of this study was to investigate VEGFR2-targeted artemisinin (ARS)-type compounds for cancer treatment. Here, we reported the ARS derivative FO-ARS-123 as a novel VEGFR2 inhibitor, which displayed potent binding activity with VEGFR2 in in silico by molecular docking (pKi, 0.40 ± 0.31 nM) and in vitro by microscale thermophoresis (Kd, 1.325 ± 0.055 μM). In addition, compound FO-ARS-123 displayed a strong inhibition on cell proliferation of a broad range of cancer cells as well as suppressed cell migration and invasion. Remarkably, FO-ARS-123 exerted profound anti-angiogenesis effects in the in vitro tube formation assay and in vivo CAM assay. These results suggest that FO-ARS-123 might be a novel and promising anti-angiogenesis agent for cancer treatment.

Addresses

Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University Mainz, Staudinger Weg 5, 55128, Mainz, Germany.

Autoren

Xiaohua Lu
Mohamed Elbadawi
Sebastian Blatt
Mohamed EM Saeed
Xiaolin Xiao
Xiao Ma
Edmond Fleischer
Peer W Kämmerer
Thomas Efferth

DOI

10.1016/j.cbi.2022.110062

eISSN

1872-7786

Externe Identifier

PubMed Identifier: 35917945

Open access

false

ISSN

0009-2797

Zeitschrift

Chemico-biological interactions

Schlüsselwörter

Humans
Neoplasms
Neovascularization, Pathologic
Artemisinins
Vascular Endothelial Growth Factor Receptor-2
Angiogenesis Inhibitors
Vascular Endothelial Growth Factor A
Cell Proliferation
Cell Movement
Human Umbilical Vein Endothelial Cells
Molecular Docking Simulation

Sprache

eng

Medium

Print-Electronic

Online publication date

2022

Paginierung

110062

Datum der Veröffentlichung

2022

Status

Published

Datum der Datenerfassung

2022

Titel

Artemisinin derivative FO-ARS-123 as a novel VEGFR2 inhibitor suppresses angiogenesis, cell migration, and invasion.

Sub types

Journal Article

Ausgabe der Zeitschrift

365

Data source: Europe PubMed Central

Abstract

Anti-angiogenesis targeting vascular endothelial growth factor receptor 2 (VEGFR2) has been considered an important strategy for cancer therapy. VEGFR2 inhibitors targeting tumor angiogenic pathways have been widely used in clinical cancer treatment. However, inherent or acquired resistance to anti-angiogenic drugs may occur and thus limit their clinical application. New VEGFR2 inhibitors are still highly demanded. The aim of this study was to investigate VEGFR2-targeted artemisinin (ARS)-type compounds for cancer treatment. Here, we reported the ARS derivative FO-ARS-123 as a novel VEGFR2 inhibitor, which displayed potent binding activity with VEGFR2 in in silico by molecular docking (pKi, 0.40 ± 0.31 nM) and in vitro by microscale thermophoresis (Kd, 1.325 ± 0.055 μM). In addition, compound FO-ARS-123 displayed a strong inhibition on cell proliferation of a broad range of cancer cells as well as suppressed cell migration and invasion. Remarkably, FO-ARS-123 exerted profound anti-angiogenesis effects in the in vitro tube formation assay and in vivo CAM assay. These results suggest that FO-ARS-123 might be a novel and promising anti-angiogenesis agent for cancer treatment.

Date of acceptance

2022

Autoren

Xiaohua Lu
Mohamed Elbadawi
Sebastian Blatt
Mohamed EM Saeed
Xiaolin Xiao
Xiao Ma
Edmond Fleischer
Peer W Kämmerer
Thomas Efferth

Autoren-URL

https://www.ncbi.nlm.nih.gov/pubmed/35917945

DOI

10.1016/j.cbi.2022.110062

eISSN

1872-7786

Zeitschrift

Chem Biol Interact

Schlüsselwörter

Angiogenesis
Artemisinin derivative
CAM assay
Cell invasion
Cell migration
VEGFR2
Angiogenesis Inhibitors
Artemisinins
Cell Movement
Cell Proliferation
Human Umbilical Vein Endothelial Cells
Humans
Molecular Docking Simulation
Neoplasms
Neovascularization, Pathologic
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factor Receptor-2

Sprache

eng

Country

Ireland

Paginierung

110062

PII

S0009-2797(22)00267-8

Datum der Veröffentlichung

2022

Status

Published

Datum, an dem der Datensatz öffentlich gemacht wurde

2022

Titel

Artemisinin derivative FO-ARS-123 as a novel VEGFR2 inhibitor suppresses angiogenesis, cell migration, and invasion.

Sub types

Journal Article

Ausgabe der Zeitschrift

365

Data source: PubMed

Artemisinin derivative FO-ARS-123 as a novel VEGFR2 inhibitor suppresses angiogenesis, cell migration, and invasion

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