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FASCAPLYSIN as a Specific Inhibitor for CDK4: Insights from Molecular Modelling.

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posted on 24.10.2012, 08:57 by M. I. Shafiq, T. Steinbrecher, R. Schmid
Cyclin-dependent kinases (CDKs) play a key role in the cell cycle and are important anti-cancer drug targets. The natural product fascaplysin inhibits CDK4 with surprising selectivity (IC(50) = 0.4 µM) compared to the close homolog CDK2 (IC(50) = 500 µM). Free energy calculations of the positively charged fascaplysin and an uncharged iso-electronic derivative in the CDK2 and CDK4 inhibitor complexes indicate that the positive charge of fascaplysin is crucial for selectivity. This finding will guide further improvements in the design of fascaplysin-based selective inhibitors for CDK4.

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PLoS ONE, 2012, 7 (8), p. e42612

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VoR (Version of Record)

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PLoS ONE

Publisher

Public Library of Science

eissn

1932-6203

Copyright date

2012

Available date

24/10/2012

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0042612

Language

eng

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