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Discovery and computer aided potency optimization of a novel class of small molecule CXCR4 antagonists.
- Source :
-
PloS one [PLoS One] 2013 Oct 18; Vol. 8 (10), pp. e78744. Date of Electronic Publication: 2013 Oct 18 (Print Publication: 2013). - Publication Year :
- 2013
-
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.
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 8
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 24205302
- Full Text :
- https://doi.org/10.1371/journal.pone.0078744