Linked Life Data

19472268

Source:http://linkedlifedata.com/resource/pubmed/id/19472268

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2009-8-5
pubmed:abstractText
Plasmepsins (PMs) are essential proteases of the plasmodia parasites and are therefore promising targets for developing drugs against malaria. We have discovered six inhibitors of PM II by high-throughput fragment-based docking of a diversity set of approximately 40,000 molecules, and consensus scoring with force field energy functions. Using the common scaffold of the three most active inhibitors (IC(50)=2-5 microM), another seven inhibitors were identified by substructure search. Furthermore, these 13 inhibitors belong to at least three different classes of compounds. The in silico approach was very effective since a total of 13 active compounds were discovered by testing only 59 molecules in an enzymatic assay. This hit rate is about one to two orders of magnitude higher than those reported for medium- and high-throughput screening techniques in vitro. Interestingly, one of the inhibitors identified by docking was halofantrine, an antimalarial drug of unknown mechanism. Explicit water molecular dynamics simulations were used to discriminate between two putative binding modes of halofantrine in PM II.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1860-7187
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
4
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1317-26
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Discovery of plasmepsin inhibitors by fragment-based docking and consensus scoring.
pubmed:affiliation
Department of Biochemistry, University of Zürich, CH-8057 Zürich, Switzerland.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't