%0 Journal Article
%T Zelnorm, an agonist of 5-Hydroxytryptamine 4-receptor, acts as a potential antitumor drug by targeting JAK/STAT3 signaling.
%A Zhang L
%A Song Q
%A Zhang X
%A Li L
%A Xu X
%A Xu X
%A Li X
%A Wang Z
%A Lin Y
%A Li X
%A Li M
%A Su F
%A Wang X
%A Qiu P
%A Guan H
%A Tang Y
%A Xu W
%A Yang J
%A Zhao C
%J Invest New Drugs
%V 38
%N 2
%D 04 2020
%M 31087223
%F 3.651
%R 10.1007/s10637-019-00790-8
%X 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.