2ofu

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[[Image:2ofu.gif|left|200px]]
[[Image:2ofu.gif|left|200px]]
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{{Structure
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<!--
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|PDB= 2ofu |SIZE=350|CAPTION= <scene name='initialview01'>2ofu</scene>, resolution 2.00&Aring;
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The line below this paragraph, containing "STRUCTURE_2ofu", 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=1N9:2,6-DIMETHYLPHENYL+2-(3,5-DIMETHOXY-4-(3-(4-METHYLPIPERAZIN-1-YL)PROPOXY)PHENYLAMINO)PYRIMIDIN-+4-YL(2,4-DIMETHOXYPHENYL)CARBAMATE'>1N9</scene>, <scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_protein-tyrosine_kinase Non-specific protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.2 2.7.10.2] </span>
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or leave the SCENE parameter empty for the default display.
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|GENE= LCK ([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_2ofu| PDB=2ofu | 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=2ofu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ofu OCA], [http://www.ebi.ac.uk/pdbsum/2ofu PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2ofu RCSB]</span>
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}}
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'''x-ray crystal structure of 2-aminopyrimidine carbamate 43 bound to Lck'''
'''x-ray crystal structure of 2-aminopyrimidine carbamate 43 bound to Lck'''
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[[Category: Single protein]]
[[Category: Single protein]]
[[Category: Huang, X.]]
[[Category: Huang, X.]]
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[[Category: kinase domain]]
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[[Category: Kinase domain]]
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[[Category: lck]]
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[[Category: Lck]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 10:49:11 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 04:17:11 2008''
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Revision as of 07:49, 4 May 2008

Image:2ofu.gif

Template:STRUCTURE 2ofu

x-ray crystal structure of 2-aminopyrimidine carbamate 43 bound to Lck


Contents

Overview

The lymphocyte-specific kinase (Lck) is a cytoplasmic tyrosine kinase of the Src family expressed in T cells and NK cells. Genetic evidence in both mice and humans demonstrates that Lck kinase activity is critical for signaling mediated by the T cell receptor (TCR), which leads to normal T cell development and activation. A small molecule inhibitor of Lck is expected to be useful in the treatment of T cell-mediated autoimmune and inflammatory disorders and/or organ transplant rejection. In this paper, we describe the synthesis, structure-activity relationships, and pharmacological characterization of 2-aminopyrimidine carbamates, a new class of compounds with potent and selective inhibition of Lck. The most promising compound of this series, 2,6-dimethylphenyl 2-((3,5-bis(methyloxy)-4-((3-(4-methyl-1-piperazinyl)propyl)oxy)phenyl)ami no)-4-pyrimidinyl(2,4-bis(methyloxy)phenyl)carbamate (43) exhibits good activity when evaluated in in vitro assays and in an in vivo model of T cell activation.

Disease

Known disease associated with this structure: SCID due to LCK deficiency OMIM:[153390]

About this Structure

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

Reference

Novel 2-aminopyrimidine carbamates as potent and orally active inhibitors of Lck: synthesis, SAR, and in vivo antiinflammatory activity., Martin MW, Newcomb J, Nunes JJ, McGowan DC, Armistead DM, Boucher C, Buchanan JL, Buckner W, Chai L, Elbaum D, Epstein LF, Faust T, Flynn S, Gallant P, Gore A, Gu Y, Hsieh F, Huang X, Lee JH, Metz D, Middleton S, Mohn D, Morgenstern K, Morrison MJ, Novak PM, Oliveira-dos-Santos A, Powers D, Rose P, Schneider S, Sell S, Tudor Y, Turci SM, Welcher AA, White RD, Zack D, Zhao H, Zhu L, Zhu X, Ghiron C, Amouzegh P, Ermann M, Jenkins J, Johnston D, Napier S, Power E, J Med Chem. 2006 Aug 10;49(16):4981-91. PMID:16884310 Page seeded by OCA on Sun May 4 10:49:11 2008

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OCA

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