2. Academic Validation
  3. Discovery of 4,6-bis(benzyloxy)-3-phenylbenzofuran as a novel Pin1 inhibitor to suppress hepatocellular carcinoma via upregulating microRNA biogenesis

Discovery of 4,6-bis(benzyloxy)-3-phenylbenzofuran as a novel Pin1 inhibitor to suppress hepatocellular carcinoma via upregulating microRNA biogenesis

  • Bioorg Med Chem. 2019 Jun 1;27(11):2235-2244. doi: 10.1016/j.bmc.2019.04.028.
Xin Fan 1,  Huaiyu He 1,  Jiao Li 1,  Guoyong Luo 2,  Yuanyuan Zheng 1,  Jian-Kang Zhou 1,  Juan He 1,  Wenchen Pu 3,  Yun Zhao 4
Affiliations

Affiliations

  • 1 Key Laboratory of Bio-Resource and Eco-Environment of Ministry of Education, College of Life Sciences, Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China.
  • 2 Guiyang College of Traditional Chinese Medicine, Guiyang 550025, China.
  • 3 Key Laboratory of Bio-Resource and Eco-Environment of Ministry of Education, College of Life Sciences, Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China. Electronic address: pu_vincent@scu.edu.cn.
  • 4 Key Laboratory of Bio-Resource and Eco-Environment of Ministry of Education, College of Life Sciences, Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China. Electronic address: zhaoyun@scu.edu.cn.
PMID: 31027708 DOI: 10.1016/j.bmc.2019.04.028
Abstract

Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) participates in diverse cancer-associated signaling pathways, playing an oncogenic role in multiple human cancers, including hepatocellular carcinoma (HCC). Our recent works clarify that PIN1 modulates miRNAs biogenesis by interacting with ERK-phosphorylated exportin-5 (XPO5) and changing XPO5 conformation, giving a potential target for HCC treatment. Herein, we discover 4,6-bis(benzyloxy)-3-phenylbenzofuran (TAB29) as a novel PIN1 Inhibitor that targets PIN1 PPIase domain. TAB29 potently inhibits PIN1 activity with the IC50 value of 874 nM and displays an excellent selectivity toward PIN1 in vitro. Cell-based biological evaluation reveals that TAB29 significantly suppresses cell proliferation of HCC cells through restoring the nucleus-to-cytoplasm export of XPO5 and upregulating mature miRNAs expression. Collectively, this work provides a promising small molecule lead compound for PIN1 inhibition, highlighting the therapeutic potential of miRNA-based treatment for human cancers.

Keywords

Benzofuran; Hepatocellular carcinoma; Pin1; XPO5; microRNA.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-128592
    Pin1 Inhibitor