Talin modulation by a synthetic N-acylurea derivative reduces angiogenesis in human endothelial cells

I. Rang Lim, Hyung Joon Joo, Minseon Jeong, Jong Ho Kim, Seung Cheol Choi, Chungho Kim, Jong Wha Jung, Soon Jun Hong

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5 Citations (Scopus)


Talin is a focal adhesion protein that activates integrins and recruits other focal adhesion proteins. Talin regulates the interactions between integrins and the extracellular matrix, which are critical for endothelial cells during angiogenesis. In this study, we successfully synthesized a novel talin modulator, N-((2-(1H-indol-3-yl)ethyl)carbamoyl)-2-(benzo[d][1,3]dioxol-5-yloxy)acetamide, referred to as KCH-1521. KCH-1521 was determined to bind talin and modulate downstream signaling molecules of talin. After 24 h of treatment, KCH-1521 changed the cell morphology of human umbilical vein endothelial cells (HUVECs) and reduced focal adhesion protein expression including vinculin and paxillin. Talin downstream signaling is regulated via focal adhesion kinase (FAK), kinase B (AKT), and extracellular signal-regulated kinase (ERK) pathways, however, treatment with KCH-1521 decreased phosphorylation of FAK, AKT, and ERK, leading to reduction of cell proliferation, survival, and angiogenesis. Interestingly, the expression of various angiogenic genes was significantly decreased after treatment with KCH-1521. Also, in vitro tube forming assay revealed that KCH-1521 reduced angiogenic networks in a time-dependent manner. To investigate the reversibility of its effects, KCH-1521 was removed after treatment. HUVECs recovered their morphology through rearrangement of the cytoskeleton and the expression of angiogenic genes was also recovered. By further optimization and in vivo studies of KCH-1521, a novel drug of talin modulation could be used to achieve therapeutic anti-angiogenesis for vascular diseases and cancers.

Original languageEnglish
Article number221
JournalInternational journal of molecular sciences
Issue number1
Publication statusPublished - 2017 Jan 22

Bibliographical note

Funding Information:
The authors thank Chi-Yeon Park and Ji-Hyun Choi from Korea University for their technical assistance. This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare (Grant number: HI14C0209), and by a grant of the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (No. NRF-2014R1A2A1A11051998), Korea.

Publisher Copyright:
© 2017 by the authors; licensee MDPI, Basel, Switzerland.


  • Anti-angiogenesis
  • Focal adhesion
  • KCH-1521
  • Talin
  • Talin modulator

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry


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