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

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

Authors :
Ronald Shin
N. Rama Krishna
Wei Zhang
Kaiyu Yuan
Ywh-Min Tzou
Sarah K. Bailey
Lalita A. Shevde
Yabing Chen
Raj K. Singh
Source :
Bioorganic & Medicinal Chemistry Letters. 26:1237-1244
Publication Year :
2016
Publisher :
Elsevier BV, 2016.

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.

Details

ISSN :
0960894X
Volume :
26
Database :
OpenAIRE
Journal :
Bioorganic & Medicinal Chemistry Letters
Accession number :
edsair.doi.dedup.....ce3ec45de30dd8402e29c37a545f6615
Full Text :
https://doi.org/10.1016/j.bmcl.2016.01.027