Identification of initial leads directed at the calmodulin-binding region on the Src-SH2 domain that exhibit anti-proliferation activity against pancreatic cancer

Ywh Min Tzou, Sarah K. Bailey, Kaiyu Yuan, Ronald Shin, Wei Zhang, Yabing Chen, Raj K. Singh, Lalita A. Shevde, N. Rama Krishna

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Cellular calmodulin binds to the SH2 domain of Src kinase, and upon Fas activation it recruits Src into the death-inducing signaling complex. This results in Src-ERK activation of cell survival pathway through which pancreatic cancer cells survive and proliferate. We had proposed that the inhibition of the interaction of calmodulin with Src-SH2 domain is an attractive strategy to inhibit the proliferation of pancreatic cancer. Thus we have performed screening of compound libraries by a combination of methods and identified some compounds (initial leads) that target the calmodulin-binding region on the SH2 domain and inhibit the proliferation of pancreatic cancer cells in in vitro assays. Most of these compounds also exhibited varying degrees of cytotoxicity when tested against immortalized breast epithelial cell line (MCF10A). These initial leads are likely candidates for development in targeted delivery of compounds to cancer cells without affecting normal cells.

Original languageEnglish (US)
Pages (from-to)1237-1244
Number of pages8
JournalBioorganic and Medicinal Chemistry Letters
Volume26
Issue number4
DOIs
StatePublished - Feb 15 2016
Externally publishedYes

Keywords

  • 3D-microtumors
  • AsPC-1
  • BxPC-3
  • ITC
  • Inhibitors
  • Initial leads
  • MCF10A
  • MiaPaCa-2
  • NMR
  • Pancreatic cancer

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Fingerprint

Dive into the research topics of 'Identification of initial leads directed at the calmodulin-binding region on the Src-SH2 domain that exhibit anti-proliferation activity against pancreatic cancer'. Together they form a unique fingerprint.

Cite this