2hog: Difference between revisions

Revision as of 06:31, 4 May 2008

crystal structure of Chek1 in complex with inhibitor 20

OverviewOverview

The development of 3-(indol-2-yl)indazoles as inhibitors of Chek1 kinase is described. Introduction of amides and heteroaryl groups at the C6 position of the indazole ring system provided sufficient Chek1 potency and selectivity over Cdk7 to permit escape from DNA damage-induced arrest in a cellular assay. Enzyme potency against Chek1 was optimized by the incorporation of a hydroxymethyl triazole moiety in compound 21 (Chek1 IC(50)=0.30nM) that was shown by X-ray crystallography to displace one of three highly conserved water molecules in the HI region of the ATP-binding cleft.

About this StructureAbout this Structure

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

ReferenceReference

3-(Indol-2-yl)indazoles as Chek1 kinase inhibitors: Optimization of potency and selectivity via substitution at C6., Fraley ME, Steen JT, Brnardic EJ, Arrington KL, Spencer KL, Hanney BA, Kim Y, Hartman GD, Stirdivant SM, Drakas BA, Rickert K, Walsh ES, Hamilton K, Buser CA, Hardwick J, Tao W, Beck SC, Mao X, Lobell RB, Sepp-Lorenzino L, Yan Y, Ikuta M, Munshi SK, Kuo LC, Kreatsoulas C, Bioorg Med Chem Lett. 2006 Dec 1;16(23):6049-53. Epub 2006 Sep 15. PMID:16978863 Page seeded by OCA on Sun May 4 06:31:12 2008

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OCA

@@ Line 1: / Line 1: @@
 [[Image:2hog.jpg|left|200px]]
- {{Structure
+<!--
-|PDB= 2hog |SIZE=350|CAPTION= <scene name='initialview01'>2hog</scene>, resolution 1.9&Aring;
+The line below this paragraph, containing "STRUCTURE_2hog", creates the "Structure Box" on the page.
-|SITE=
+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|LIGAND= <scene name='pdbligand=710:(5-{3-[5-(PIPERIDIN-1-YLMETHYL)-1H-INDOL-2-YL]-1H-INDAZOL-6-YL}-2H-1,2,3-TRIAZOL-4-YL)METHANOL'>710</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_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span>
+or leave the SCENE parameter empty for the default display.
-|GENE= CHEK1, CHK1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
+-->
-|DOMAIN=
+{{STRUCTURE_2hog|  PDB=2hog  |  SCENE=  }}
-|RELATEDENTRY=
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2hog FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hog OCA], [http://www.ebi.ac.uk/pdbsum/2hog PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2hog RCSB]</span>
-}}
 '''crystal structure of Chek1 in complex with inhibitor 20'''
@@ Line 28: / Line 25: @@
 [[Category: Ikuta, M.]]
 [[Category: Yan, Y.]]
-[[Category: cell cycle checkpoint]]
+[[Category: Cell cycle checkpoint]]
-[[Category: chek1]]
+[[Category: Chek1]]
-[[Category: kinase]]
+[[Category: Kinase]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 06:31:12 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 03:33:06 2008''