Development of a new Ca2+/calmodulin antagonist and its anti-proliferative activity against colorectal cancer cells

Joong Sup Shim, Jiyong Lee, Kyung Noo Kim, Ho Jeong Kwon

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17 Citations (Scopus)

Abstract

We previously identified a cellular target of a cell cycle inhibitor HBC as Ca2+/calmodulin (Ca2+/CaM) through chemical genetics approach. Using the mechanism-based drug design, we developed a new Ca2+/CaM antagonists based on the structure of HBC. The compound, (4-{3,5-bis-[2-(4-hydroxy-3-methoxy-phenyl)-vinyl]-4,5-dihydro-pyrazol-1-yl}-phenyl)-(4-methyl-piperazin-1-yl)-methanone (referred as HBCP), binds to Ca2+/CaM in vitro and inhibits the proliferation of HCT15 colon cancer cells. HBCP induced sustained phosphorylation of ERK1/2 and subsequently activated p21WAF1 expression in HCT15 cells. Moreover, HBCP reversibly induced the G0/G1 cell cycle arrest in the cells. These data demonstrate that HBCP is a new potent Ca2+/CaM antagonist and can be applied for CaM related therapeutic uses.

Original languageEnglish
Pages (from-to)747-751
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume359
Issue number3
DOIs
Publication statusPublished - 2007 Aug 3

Bibliographical note

Funding Information:
We are grateful to Drs. J.M. Kim and W.J. Lee of Digital Genomics for their valuable comments. This study was partially supported by grants from the Chemical Genomics program and the National Research Laboratory from the Korean Ministry of Science and Technology and from the Brain Korea 21 Project, Republic of Korea.

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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