3bz3

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
(New page: 200px {{Structure |PDB= 3bz3 |SIZE=350|CAPTION= <scene name='initialview01'>3bz3</scene>, resolution 2.200&Aring; |SITE= <scene name='pdbsite=AC1:Yam+Binding+Site...)
Line 1: Line 1:
[[Image:3bz3.jpg|left|200px]]
[[Image:3bz3.jpg|left|200px]]
-
{{Structure
+
<!--
-
|PDB= 3bz3 |SIZE=350|CAPTION= <scene name='initialview01'>3bz3</scene>, resolution 2.200&Aring;
+
The line below this paragraph, containing "STRUCTURE_3bz3", creates the "Structure Box" on the page.
-
|SITE= <scene name='pdbsite=AC1:Yam+Binding+Site+For+Residue+A+1'>AC1</scene>
+
You may change the PDB parameter (which sets the PDB file loaded into the applet)
-
|LIGAND= <scene name='pdbligand=YAM:N-METHYL-N-{3-[({2-[(2-OXO-2,3-DIHYDRO-1H-INDOL-5-YL)AMINO]-5-(TRIFLUOROMETHYL)PYRIMIDIN-4-YL}AMINO)METHYL]PYRIDIN-2-YL}METHANESULFONAMIDE'>YAM</scene>
+
or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-
|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>
+
or leave the SCENE parameter empty for the default display.
-
|GENE= PTK2, FAK, FAK1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
+
-->
-
|DOMAIN=<span class='plainlinks'>[http://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=smart00220 S_TKc], [http://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=cd05056 PTKc_FAK]</span>
+
{{STRUCTURE_3bz3| PDB=3bz3 | SCENE= }}
-
|RELATEDENTRY=
+
-
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3bz3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bz3 OCA], [http://www.ebi.ac.uk/pdbsum/3bz3 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=3bz3 RCSB]</span>
+
-
}}
+
'''Crystal Structure Analysis of Focal Adhesion Kinase with a Methanesulfonamide Diaminopyrimidine Inhibitor'''
'''Crystal Structure Analysis of Focal Adhesion Kinase with a Methanesulfonamide Diaminopyrimidine Inhibitor'''
Line 28: Line 25:
[[Category: Marr, E.]]
[[Category: Marr, E.]]
[[Category: Vajdos, F.]]
[[Category: Vajdos, F.]]
-
[[Category: acetylation]]
+
[[Category: Acetylation]]
-
[[Category: alternative splicing]]
+
[[Category: Alternative splicing]]
-
[[Category: atp-binding]]
+
[[Category: Atp-binding]]
-
[[Category: cell junction]]
+
[[Category: Cell junction]]
-
[[Category: dfg-helix]]
+
[[Category: Dfg-helix]]
-
[[Category: kinase]]
+
[[Category: Kinase]]
-
[[Category: nucleotide-binding]]
+
[[Category: Nucleotide-binding]]
-
[[Category: phosphoprotein]]
+
[[Category: Phosphoprotein]]
-
[[Category: transferase]]
+
[[Category: Transferase]]
-
[[Category: tyrosine-protein kinase]]
+
[[Category: Tyrosine-protein kinase]]
-
 
+
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 21:13:08 2008''
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Apr 2 11:59:48 2008''
+

Revision as of 18:13, 4 May 2008

Image:3bz3.jpg

Template:STRUCTURE 3bz3

Crystal Structure Analysis of Focal Adhesion Kinase with a Methanesulfonamide Diaminopyrimidine Inhibitor


Overview

Cancer cells are characterized by the ability to grow in an anchorage-independent manner. The activity of the nonreceptor tyrosine kinase, focal adhesion kinase (FAK), is thought to contribute to this phenotype. FAK localizes in focal adhesion plaques and has a role as a scaffolding and signaling protein for other adhesion molecules. Recent studies show a strong correlation between increased FAK expression and phosphorylation status and the invasive phenotype of aggressive human tumors. PF-562,271 is a potent, ATP-competitive, reversible inhibitor of FAK and Pyk2 catalytic activity with a IC(50) of 1.5 and 14 nmol/L, respectively. Additionally, PF-562,271 displayed robust inhibition in an inducible cell-based assay measuring phospho-FAK with an IC(50) of 5 nmol/L. PF-562,271 was evaluated against multiple kinases and displays >100x selectivity against a long list of nontarget kinases. PF-562,271 inhibits FAK phosphorylation in vivo in a dose-dependent fashion (calculated EC(50) of 93 ng/mL, total) after p.o. administration to tumor-bearing mice. In vivo inhibition of FAK phosphorylation (>50%) was sustained for >4 hours with a single p.o. dose of 33 mg/kg. Antitumor efficacy and regressions were observed in multiple human s.c. xenograft models. No weight loss, morbidity, or mortality were observed in any in vivo experiment. Tumor growth inhibition was dose and drug exposure dependent. Taken together, these data show that kinase inhibition with an ATP-competitive small molecule inhibitor of FAK decreases the phospho-status in vivo, resulting in robust antitumor activity.

About this Structure

3BZ3 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Antitumor activity and pharmacology of a selective focal adhesion kinase inhibitor, PF-562,271., Roberts WG, Ung E, Whalen P, Cooper B, Hulford C, Autry C, Richter D, Emerson E, Lin J, Kath J, Coleman K, Yao L, Martinez-Alsina L, Lorenzen M, Berliner M, Luzzio M, Patel N, Schmitt E, LaGreca S, Jani J, Wessel M, Marr E, Griffor M, Vajdos F, Cancer Res. 2008 Mar 15;68(6):1935-44. PMID:18339875 Page seeded by OCA on Sun May 4 21:13:08 2008

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3bz3"
Personal tools