Zelnorm, an agonist of 5-Hydroxytryptamine 4-receptor, acts as a potential antitumor drug by targeting JAK/STAT3 signaling.
Invest New Drugs
; 38(2): 311-320, 2020 04.
Article
en En
| MEDLINE
| ID: mdl-31087223
ABSTRACT
The Janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) signaling pathway plays central roles in cancer cell growth and survival. Drug repurposing strategies have provided a valuable approach for developing antitumor drugs. Zelnorm (tegaserod maleate) was originally designed as an agonist of 5-hydroxytryptamine 4 receptor (5-HT4R) and approved by the FDA for treating irritable bowel syndrome with constipation (IBS-C). Through the use of a high-throughput drug screening system, Zelnorm was identified as a JAK/STAT3 signaling inhibitor. Moreover, the inhibition of STAT3 phosphorylation by Zelnorm was independent of its original target 5-HT4R. Zelnorm could cause G1 cell cycle arrest, induce cell apoptosis and inhibit the growth of a variety of cancer cells. The present study identifies Zelnorm as a novel JAK/STAT3 signaling inhibitor and reveals a new clinical application of Zelnorm upon market reintroduction.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Inhibidores de Proteínas Quinasas
/
Factor de Transcripción STAT3
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Quinasas Janus
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Agonistas del Receptor de Serotonina 5-HT4
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Indoles
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Neoplasias
/
Antineoplásicos
Tipo de estudio:
Prognostic_studies
Límite:
Animals
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Humans
Idioma:
En
Revista:
Invest New Drugs
Año:
2020
Tipo del documento:
Article
País de afiliación:
China