2fme

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[[Image:2fme.gif|left|200px]]
[[Image:2fme.gif|left|200px]]
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{{Structure
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<!--
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|PDB= 2fme |SIZE=350|CAPTION= <scene name='initialview01'>2fme</scene>, resolution 2.10&Aring;
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The line below this paragraph, containing "STRUCTURE_2fme", creates the "Structure Box" on the page.
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|SITE=
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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|LIGAND= <scene name='pdbligand=3QC:(4R)-4-(3-HYDROXYPHENYL)-N,N,7,8-TETRAMETHYL-3,4-DIHYDROISOQUINOLINE-2(1H)-CARBOXAMIDE'>3QC</scene>, <scene name='pdbligand=ADP:ADENOSINE-5&#39;-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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|ACTIVITY=
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|GENE= KIF11, EG5, KNSL1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
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|DOMAIN=
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{{STRUCTURE_2fme| PDB=2fme | SCENE= }}
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|RELATEDENTRY=
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2fme FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2fme OCA], [http://www.ebi.ac.uk/pdbsum/2fme PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2fme RCSB]</span>
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'''Crystal structure of the mitotic kinesin eg5 (ksp) in complex with mg-adp and (r)-4-(3-hydroxyphenyl)-n,n,7,8-tetramethyl-3,4-dihydroisoquinoline-2(1h)-carboxamide'''
'''Crystal structure of the mitotic kinesin eg5 (ksp) in complex with mg-adp and (r)-4-(3-hydroxyphenyl)-n,n,7,8-tetramethyl-3,4-dihydroisoquinoline-2(1h)-carboxamide'''
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[[Category: Single protein]]
[[Category: Single protein]]
[[Category: Sheriff, S.]]
[[Category: Sheriff, S.]]
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[[Category: eg5 ksp mg-adp complex inhibitor]]
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[[Category: Eg5 ksp mg-adp complex inhibitor]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 04:04:08 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 03:04:47 2008''
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Revision as of 01:04, 4 May 2008

Template:STRUCTURE 2fme

Crystal structure of the mitotic kinesin eg5 (ksp) in complex with mg-adp and (r)-4-(3-hydroxyphenyl)-n,n,7,8-tetramethyl-3,4-dihydroisoquinoline-2(1h)-carboxamide


Overview

In a high-throughput screening effort, a series of tetrahydroisoquinolines was identified as modest inhibitors of human Eg5. A medicinal chemistry optimization effort led to the identification of R-4-(3-hydroxyphenyl)-N,N-7,8-tetramethyl-3,4-dihydroisoquinoline-2(1H)-ca rboxamide (32a) as a potent inhibitor of human Eg5 (ATPase IC50 104 nM) with good anti-proliferative activity in A2780 cells (IC50 234 nM).

About this Structure

2FME is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Inhibitors of human mitotic kinesin Eg5: characterization of the 4-phenyl-tetrahydroisoquinoline lead series., Tarby CM, Kaltenbach RF 3rd, Huynh T, Pudzianowski A, Shen H, Ortega-Nanos M, Sheriff S, Newitt JA, McDonnell PA, Burford N, Fairchild CR, Vaccaro W, Chen Z, Borzilleri RM, Naglich J, Lombardo LJ, Gottardis M, Trainor GL, Roussell DL, Bioorg Med Chem Lett. 2006 Apr 15;16(8):2095-100. Epub 2006 Feb 3. PMID:16458511 Page seeded by OCA on Sun May 4 04:04:08 2008

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