Back to Search
Start Over
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
- 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.
- Subjects :
- 0301 basic medicine
Calmodulin
Cell Survival
Clinical Biochemistry
Pharmaceutical Science
Antineoplastic Agents
Plasma protein binding
Calorimetry
SH2 domain
Biochemistry
Article
src Homology Domains
03 medical and health sciences
0302 clinical medicine
Cell Line, Tumor
Pancreatic cancer
Drug Discovery
medicine
Humans
Cytotoxicity
Nuclear Magnetic Resonance, Biomolecular
Molecular Biology
biology
Chemistry
Organic Chemistry
In vitro toxicology
medicine.disease
Cell biology
Pancreatic Neoplasms
src-Family Kinases
030104 developmental biology
030220 oncology & carcinogenesis
Cancer cell
Immunology
biology.protein
Molecular Medicine
Protein Binding
Proto-oncogene tyrosine-protein kinase Src
Subjects
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