HIF-1α suppressing small molecule, LW6, inhibits cancer cell growth by binding to calcineurin b homologous protein 1

Beom Seok Kim, Kyeong Lee, Hye Jin Jung, Deepak Bhattarai, Ho Jeong Kwon

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24 Citations (Scopus)


Hypoxia inducible factor-1 alpha (HIF-1α) plays an important role in angiogenesis and metastasis and is a promising therapeutic target for the development of anti-cancer drugs. We recently developed a new synthetic small molecule inhibitor of HIF-1α, LW6, which results in inhibition of angiogenesis. To investigate its underlying mechanism, target protein identification was conducted by reverse chemical proteomics using phage display. We identified calcineurin b homologous protein 1 (CHP1) as a target protein of LW6, which specifically binds to CHP1 in a Ca2+ dependent manner. Covalent labeling of LW6 using photoaffinity and click chemistry demonstrated its co-localization with CHP1 in live cells. HIF-1α was decreased by CHP1 knockdown in HepG2 cells, and angiogenesis was not induced in HUVEC cells by treatment with conditioned media from CHP1 knockdown cells compared to the control. These data demonstrated that LW6 inhibited HIF-1α stability via direct binding with CHP1 resulting in suppression of angiogenesis, providing a new insight into the role of CHP1 in HIF-1α regulation. LW6 could serve as a new chemical probe to explore CHP1 function.

Original languageEnglish
Pages (from-to)14-20
Number of pages7
JournalBiochemical and Biophysical Research Communications
Issue number1
Publication statusPublished - 2015 Feb 27

Bibliographical note

Funding Information:
This study was partly supported by grants from the National Research Foundation of Korea funded by the Korean Government ( 2010-0017984 , 2012M3A9D1054520 , 2014R1A2A2A01005455 ), the Translational Research Center for Protein Function Control, KRF ( 2009–0083522 ) and the Brain Korea 21 Plus Project , Republic of Korea.

Publisher Copyright:
© 2015 Elsevier Inc. All rights reserved.

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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