Abstract |
Amongst the chemokine signalling axes involved in cancer, chemokine CXCL12 acting on chemokine receptor CXCR4 is particularly significant since it orchestrates migration of cancer cells in a tissue-specific metastatic process. High CXCR4 tumour expression is associated with poor prognosis of lung, brain, CNS, blood and breast cancers. We have identified a new class of small molecule CXCR4 antagonists based on the use of computational modelling studies in concert with experimental determination of in vitro activity against CXCL12-induced intracellular calcium mobilisation, proliferation and chemotaxis. Molecular modelling proved to be a useful tool in rationalising our observed potencies, as well as informing the direction of the synthetic efforts aimed at producing more potent compounds.
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Authors | Victoria Vinader, Djevdet S Ahmet, Mohaned S Ahmed, Laurence H Patterson, Kamyar Afarinkia |
Journal | PloS one
(PLoS One)
Vol. 8
Issue 10
Pg. e78744
( 2013)
ISSN: 1932-6203 [Electronic] United States |
PMID | 24205302
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Receptors, CXCR4
- Small Molecule Libraries
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Topics |
- Cell Line, Tumor
- Computer Simulation
- Drug Discovery
(methods)
- Humans
- Models, Molecular
- Protein Conformation
- Receptors, CXCR4
(antagonists & inhibitors, chemistry)
- Small Molecule Libraries
(chemistry, pharmacology)
- Structure-Activity Relationship
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