2h8h

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[[Image:2h8h.gif|left|200px]]
[[Image:2h8h.gif|left|200px]]
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{{Structure
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<!--
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|PDB= 2h8h |SIZE=350|CAPTION= <scene name='initialview01'>2h8h</scene>, resolution 2.20&Aring;
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The line below this paragraph, containing "STRUCTURE_2h8h", 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=H8H:N-(5-CHLORO-1,3-BENZODIOXOL-4-YL)-7-[2-(4-METHYLPIPERAZIN-1-YL)ETHOXY]-5-(TETRAHYDRO-2H-PYRAN-4-YLOXY)QUINAZOLIN-4-AMINE'>H8H</scene>, <scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</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= SRC, SRC1 ([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_2h8h| PDB=2h8h | 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=2h8h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2h8h OCA], [http://www.ebi.ac.uk/pdbsum/2h8h PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2h8h RCSB]</span>
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}}
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'''Src kinase in complex with a quinazoline inhibitor'''
'''Src kinase in complex with a quinazoline inhibitor'''
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[[Category: Pauptit, R A.]]
[[Category: Pauptit, R A.]]
[[Category: Rowsell, S.]]
[[Category: Rowsell, S.]]
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[[Category: src kinase]]
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[[Category: Src kinase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 05:59:30 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 03:26:56 2008''
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Revision as of 02:59, 4 May 2008

Image:2h8h.gif

Template:STRUCTURE 2h8h

Src kinase in complex with a quinazoline inhibitor


Overview

Src family kinases (SFKs) are nonreceptor tyrosine kinases that are reported to be critical for cancer progression. We report here a novel subseries of C-5-substituted anilinoquinazolines that display high affinity and specificity for the tyrosine kinase domain of the c-Src and Abl enzymes. These compounds exhibit high selectivity for SFKs over a panel of recombinant protein kinases, excellent pharmacokinetics, and in vivo activity following oral dosing. N-(5-Chloro-1,3-benzodioxol-4-yl)-7-[2-(4-methylpiperazin-1-yl)ethoxy]-5-( tetrahydro-2H-pyran-4-yloxy)quinazolin-4-amine (AZD0530) inhibits c-Src and Abl enzymes at low nanomolar concentrations and is highly selective over a range of kinases. AZD0530 displays excellent pharmacokinetic parameters in animal preclinically and in man (t(1/2) = 40 h). AZD0530 is a potent inhibitor of tumor growth in a c-Src-transfected 3T3-fibroblast xenograft model in vivo and led to a significant increase in survival in a highly aggressive, orthotopic model of human pancreatic cancer when dosed orally once daily. AZD0530 is currently undergoing clinical evaluation in man.

About this Structure

2H8H is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

N-(5-chloro-1,3-benzodioxol-4-yl)-7-[2-(4-methylpiperazin-1-yl)ethoxy]-5- (tetrahydro-2H-pyran-4-yloxy)quinazolin-4-amine, a novel, highly selective, orally available, dual-specific c-Src/Abl kinase inhibitor., Hennequin LF, Allen J, Breed J, Curwen J, Fennell M, Green TP, Lambert-van der Brempt C, Morgentin R, Norman RA, Olivier A, Otterbein L, Ple PA, Warin N, Costello G, J Med Chem. 2006 Nov 2;49(22):6465-88. PMID:17064066 Page seeded by OCA on Sun May 4 05:59:30 2008

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