Fascaplysin as a specific inhibitor for CDK4: insights from molecular modelling.

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 c...

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Autores principales:	Muhammad Imtiaz Shafiq, Thomas Steinbrecher, Ralf Schmid
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c622997dbf9b4663940d1dddc8902028
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spelling	oai:doaj.org-article:c622997dbf9b4663940d1dddc89020282021-11-18T07:08:51ZFascaplysin as a specific inhibitor for CDK4: insights from molecular modelling.1932-620310.1371/journal.pone.0042612https://doaj.org/article/c622997dbf9b4663940d1dddc89020282012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22905154/?tool=EBIhttps://doaj.org/toc/1932-6203Cyclin-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.Muhammad Imtiaz ShafiqThomas SteinbrecherRalf SchmidPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 8, p e42612 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Muhammad Imtiaz Shafiq Thomas Steinbrecher Ralf Schmid Fascaplysin as a specific inhibitor for CDK4: insights from molecular modelling.
description	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.
format	article
author	Muhammad Imtiaz Shafiq Thomas Steinbrecher Ralf Schmid
author_facet	Muhammad Imtiaz Shafiq Thomas Steinbrecher Ralf Schmid
author_sort	Muhammad Imtiaz Shafiq
title	Fascaplysin as a specific inhibitor for CDK4: insights from molecular modelling.
title_short	Fascaplysin as a specific inhibitor for CDK4: insights from molecular modelling.
title_full	Fascaplysin as a specific inhibitor for CDK4: insights from molecular modelling.
title_fullStr	Fascaplysin as a specific inhibitor for CDK4: insights from molecular modelling.
title_full_unstemmed	Fascaplysin as a specific inhibitor for CDK4: insights from molecular modelling.
title_sort	fascaplysin as a specific inhibitor for cdk4: insights from molecular modelling.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/c622997dbf9b4663940d1dddc8902028
work_keys_str_mv	AT muhammadimtiazshafiq fascaplysinasaspecificinhibitorforcdk4insightsfrommolecularmodelling AT thomassteinbrecher fascaplysinasaspecificinhibitorforcdk4insightsfrommolecularmodelling AT ralfschmid fascaplysinasaspecificinhibitorforcdk4insightsfrommolecularmodelling
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Fascaplysin as a specific inhibitor for CDK4: insights from molecular modelling.

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