Linked Life Data

18503753

Source:http://linkedlifedata.com/resource/pubmed/id/18503753

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2008-6-25
pubmed:abstractText
HsEg5 is an important mitotic kinesin responsible for bipolar spindle formation at early mitosis. A rich body of evidence shows that inhibition of HsEg5 can result in mitotic arrest followed by cellular apoptosis. Recently identified HsEg5 inhibitor, CK0238273, exhibits potent antitumor activity and is currently in clinical trial. Here we report the cocrystal structure of the motor domain of HsEg5 in complex with CK0238273 at a 2.15 A resolution. Compared to the previously published HsEg5-Monastrol complex structure, CK0238273 shares the same induced-fit pocket with similar allosteric inhibitory mechanism. However, CK0238273 shows better fitting to the binding pocket with 65% increase of hydrophobic interaction area than that of Monastrol. Some unique hydrophilic interactions were also observed mostly between the phenyl ring and 8-chloro on quinazolinone of CK0238273 with ARG221 and GLY217. We believe that the combination of these interactions defines the superior potency and specificity of CK0238273.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1090-2104
pubmed:author
pubmed:issnType
Electronic
pubmed:day
8
pubmed:volume
372
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
565-70
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Crystal structure of HsEg5 in complex with clinical candidate CK0238273 provides insight into inhibitory mechanism, potency, and specificity.
pubmed:affiliation
ArQule Biomedical Institute, ArQule Incorporated, 333 Providence Highway, Norwood, MA 02062, USA. bzhang@cytrx.com
pubmed:publicationType
Journal Article