1yrs: Difference between revisions
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==Overview== | ==Overview== | ||
Optimization of high-throughput screening (HTS) hits resulted in the | Optimization of high-throughput screening (HTS) hits resulted in the discovery of 3,5-diaryl-4,5-dihydropyrazoles as potent and selective inhibitors of KSP. Dihydropyrazole 15 is a potent, cell-active KSP inhibitor that induces apoptosis and generates aberrant mitotic spindles in human ovarian carcinoma cells at low nanomolar concentrations. X-ray crystallographic evidence is presented which demonstrates that these inhibitors bind in an allosteric pocket of KSP distant from the nucleotide and microtubule binding sites. | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Breslin, M | [[Category: Breslin, M J.]] | ||
[[Category: Buser, C | [[Category: Buser, C A.]] | ||
[[Category: Coleman, P | [[Category: Coleman, P J.]] | ||
[[Category: Cox, C | [[Category: Cox, C D.]] | ||
[[Category: Hamilton, K.]] | [[Category: Hamilton, K.]] | ||
[[Category: Hartman, G | [[Category: Hartman, G D.]] | ||
[[Category: Kohl, N | [[Category: Kohl, N E.]] | ||
[[Category: Kuo, L | [[Category: Kuo, L C.]] | ||
[[Category: Mariano, B | [[Category: Mariano, B J.]] | ||
[[Category: Torrent, M.]] | [[Category: Torrent, M.]] | ||
[[Category: Walsh, E | [[Category: Walsh, E S.]] | ||
[[Category: Yan, Y.]] | [[Category: Yan, Y.]] | ||
[[Category: ADP]] | [[Category: ADP]] | ||
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[[Category: cell cycle]] | [[Category: cell cycle]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:08:31 2008'' | ||
Revision as of 17:08, 21 February 2008
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Crystal structure of KSP in complex with inhibitor 1
OverviewOverview
Optimization of high-throughput screening (HTS) hits resulted in the discovery of 3,5-diaryl-4,5-dihydropyrazoles as potent and selective inhibitors of KSP. Dihydropyrazole 15 is a potent, cell-active KSP inhibitor that induces apoptosis and generates aberrant mitotic spindles in human ovarian carcinoma cells at low nanomolar concentrations. X-ray crystallographic evidence is presented which demonstrates that these inhibitors bind in an allosteric pocket of KSP distant from the nucleotide and microtubule binding sites.
About this StructureAbout this Structure
1YRS is a Single protein structure of sequence from Homo sapiens with , and as ligands. Full crystallographic information is available from OCA.
ReferenceReference
Kinesin spindle protein (KSP) inhibitors. Part 1: The discovery of 3,5-diaryl-4,5-dihydropyrazoles as potent and selective inhibitors of the mitotic kinesin KSP., Cox CD, Breslin MJ, Mariano BJ, Coleman PJ, Buser CA, Walsh ES, Hamilton K, Huber HE, Kohl NE, Torrent M, Yan Y, Kuo LC, Hartman GD, Bioorg Med Chem Lett. 2005 Apr 15;15(8):2041-5. PMID:15808464
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