当前位置： SCI文献检索 > EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY期刊下所有文献 > Doing the methylene shuffle--further insights into the inhibition of mitotic kinesin Eg5 with S-trityl L-cysteine.

Doing the methylene shuffle--further insights into the inhibition of mitotic kinesin Eg5 with S-trityl L-cysteine.

Abstract：

:S-Trityl L-cysteine (STLC) is an inhibitor of the mitotic kinesin Eg5 with potential as an antimitotic chemotherapeutic agent. We previously reported the crystal structure of the ligand-protein complex, and now for the first time, have quantified the interactions using a molecular dynamics based approach. Based on these data, we have explored the SAR of the trityl head group using the methylene shuffle strategy to expand the occupation of one of the hydrophobic pockets. The most potent compounds exhibit strong (<100 nM) inhibition of Eg5 in the basal ATPase assay and inhibit growth in a variety of tumour-derived cell lines.

journal_name

Eur J Med Chem

journal_title

European journal of medicinal chemistry

authors

Abualhasan MN,Good JA,Wittayanarakul K,Anthony NG,Berretta G,Rath O,Kozielski F,Sutcliffe OB,Mackay SP

doi

10.1016/j.ejmech.2012.05.034

subject

Has Abstract

pub_date

2012-08-01 00:00:00

pages

483-98

eissn

0223-5234

issn

1768-3254

pii

S0223-5234(12)00345-5

journal_volume

54

pub_type

杂志文章

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