1pxm

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[[Image:1pxm.gif|left|200px]]
[[Image:1pxm.gif|left|200px]]
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{{Structure
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<!--
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|PDB= 1pxm |SIZE=350|CAPTION= <scene name='initialview01'>1pxm</scene>, resolution 2.53&Aring;
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The line below this paragraph, containing "STRUCTURE_1pxm", 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=CK5:3-[4-(2,4-DIMETHYL-THIAZOL-5-YL)-PYRIMIDIN-2-YLAMINO]-PHENOL'>CK5</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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or leave the SCENE parameter empty for the default display.
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|GENE= CDK2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
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-->
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|DOMAIN=
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{{STRUCTURE_1pxm| PDB=1pxm | SCENE= }}
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|RELATEDENTRY=[[1aq1|1AQ1]], [[1b39|1B39]], [[1ckp|1CKP]], [[1di8|1DI8]], [[1dm2|1DM2]], [[1e1v|1E1V]], [[1e1x|1E1X]], [[1e9h|1E9H]], [[1fin|1FIN]], [[1fvt|1FVT]], [[1fvv|1FVV]], [[1g5s|1G5S]], [[1gih|1GIH]], [[1gii|1GII]], [[1gij|1GIJ]], [[1gz8|1GZ8]], [[1hck|1HCK]], [[1hcl|1HCL]], [[1jsv|1JSV]], [[1jvp|1JVP]], [[1ke5|1KE5]], [[1ke6|1KE6]], [[1ke7|1KE7]], [[1ke8|1KE8]], [[1ke9|1KE9]], [[1pxn|1PXN]], [[1pxo|1PXO]], [[1pxp|1PXP]]
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1pxm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1pxm OCA], [http://www.ebi.ac.uk/pdbsum/1pxm PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1pxm RCSB]</span>
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}}
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'''HUMAN CYCLIN DEPENDENT KINASE 2 COMPLEXED WITH THE INHIBITOR 3-[4-(2,4-Dimethyl-thiazol-5-yl)-pyrimidin-2-ylamino]-phenol'''
'''HUMAN CYCLIN DEPENDENT KINASE 2 COMPLEXED WITH THE INHIBITOR 3-[4-(2,4-Dimethyl-thiazol-5-yl)-pyrimidin-2-ylamino]-phenol'''
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[[Category: Zheleva, D.]]
[[Category: Zheleva, D.]]
[[Category: 3d-structure.]]
[[Category: 3d-structure.]]
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[[Category: atp-binding]]
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[[Category: Atp-binding]]
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[[Category: cell cycle]]
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[[Category: Cell cycle]]
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[[Category: cell division]]
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[[Category: Cell division]]
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[[Category: inhibition]]
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[[Category: Inhibition]]
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[[Category: mitosis]]
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[[Category: Mitosis]]
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[[Category: phosphorylation]]
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[[Category: Phosphorylation]]
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[[Category: protein kinase]]
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[[Category: Protein kinase]]
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[[Category: serine/threonine-protein kinase]]
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[[Category: Serine/threonine-protein kinase]]
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[[Category: transferase]]
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[[Category: Transferase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 05:36:38 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 23:05:57 2008''
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Revision as of 02:36, 3 May 2008

Image:1pxm.gif

Template:STRUCTURE 1pxm

HUMAN CYCLIN DEPENDENT KINASE 2 COMPLEXED WITH THE INHIBITOR 3-[4-(2,4-Dimethyl-thiazol-5-yl)-pyrimidin-2-ylamino]-phenol


Overview

Following the identification through virtual screening of 4-(2,4-dimethyl-thiazol-5-yl)pyrimidin-2-ylamines as moderately potent inhibitors of cyclin-dependent kinase-2 (CDK2), a CDK inhibitor analogue program was initiated. The first aims were to optimize potency and to evaluate the cellular mode of action of lead candidate molecules. Here the synthetic chemistry, the structure-guided design approach, and the structure-activity relationships (SARs) that led to the discovery of 2-anilino-4-(thiazol-5-yl)pyrimidine ATP-antagonistic CDK2 inhibitors, many with very low nM K(i)s against CDK2, are reported. Furthermore, X-ray crystal structures of four representative analogues from our chemical series in complex with CDK2 are presented, and these structures are used to rationalize the observed biochemical SARs. Finally results are reported that show, using the most potent CDK2 inhibitor compound from the current series, that the observed antiproliferative and proapoptotic effects are consistent with cellular CDK2 and CDK9 inhibition.

About this Structure

1PXM is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

2-Anilino-4-(thiazol-5-yl)pyrimidine CDK inhibitors: synthesis, SAR analysis, X-ray crystallography, and biological activity., Wang S, Meades C, Wood G, Osnowski A, Anderson S, Yuill R, Thomas M, Mezna M, Jackson W, Midgley C, Griffiths G, Fleming I, Green S, McNae I, Wu SY, McInnes C, Zheleva D, Walkinshaw MD, Fischer PM, J Med Chem. 2004 Mar 25;47(7):1662-75. PMID:15027857 Page seeded by OCA on Sat May 3 05:36:38 2008

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OCA

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