{Reference Type}: Journal Article
{Title}: Zelnorm, an agonist of 5-Hydroxytryptamine 4-receptor, acts as a potential antitumor drug by targeting JAK/STAT3 signaling.
{Author}: Zhang L;Song Q;Zhang X;Li L;Xu X;Xu X;Li X;Wang Z;Lin Y;Li X;Li M;Su F;Wang X;Qiu P;Guan H;Tang Y;Xu W;Yang J;Zhao C;
{Journal}: Invest New Drugs
{Volume}: 38
{Issue}: 2
{Year}: 04 2020
{Factor}: 3.651
{DOI}: 10.1007/s10637-019-00790-8
{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.