Discovery and Computer Aided Potency Optimization of a Novel Class of Small Molecule CXCR4 Antagonists

Victoria Vinader, Djevdet S Ahmet, Mohaned S Ahmed, Laurence H Patterson and Kamyar Afarinkia

PLOS ONE, 2013, vol. 8, issue 10, 1-

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.

Date: 2013
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Persistent link: https://EconPapers.repec.org/RePEc:plo:pone00:0078744

DOI: 10.1371/journal.pone.0078744

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