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Biochemical pharmacology

Biochemical pharmacology

IF: 5.3
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Identification of a new class of activators of the Hippo pathway with antitumor activity in vitro and in vivo

Published:17 April 2024 DOI: 10.1016/j.bcp.2024.116217
Guifeng Lin , Anjie Xia , Jingxin Qiao , Hailin Zhang , Pei Chen , Pei Zhou , Qian Hu , Zhiyu Xiang , Shiyu Zhang , Linli Li , Shengyong Yang

Abstract

The Hippo pathway is a key regulator of tissue growth, organ size, and tumorigenesis. Activating the Hippo pathway by gene editing or pharmaceutical intervention has been proven to be a new therapeutic strategy for treatment of the Hippo pathway-dependent cancers. To now, a number of compounds that directly target the downstream effector proteins of Hippo pathway, including YAP and TEADs, have been disclosed, but very few Hippo pathway activators are reported. Here, we discovered a new class of Hippo pathway activator, YL-602, which inhibited CTGF expression in cells irrespective of cell density and the presence of serum. Mechanistically, YL-602 activates the Hippo pathway via MST1/2, which is different from known activators of Hippo pathway. In vitro, YL-602 significantly induced tumor cell apoptosis and inhibited colony formation of tumor cells. In vivo, oral administration of YL-602 substantially suppressed the growth of cancer cells by activation of Hippo pathway. Overall, YL-602 could be a promising lead compound, and deserves further investigation for its mechanism of action and therapeutic applications.

Substances (6)

Materials
Procduct Name CAS Molecular Formula Supplier Price
XMU-MP-1 2061980-01-4 C17H16N6O3S2 117 suppliers $17.00-$4741.00
XMU-MP-1 2061980-01-4 C17H16N6O3S2 117 suppliers $17.00-$4741.00
XMU-MP-1 2061980-01-4 C17H16N6O3S2 117 suppliers $17.00-$4741.00
XMU-MP-1 2061980-01-4 C17H16N6O3S2 117 suppliers $17.00-$4741.00
XMU-MP-1 HYDROCHLORIDE 2061980-01-4 1 suppliers Inquiry
XMU-MP-1 HYDROCHLORIDE 2061980-01-4 1 suppliers Inquiry

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