1oiu

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 1: Line 1:
-
[[Image:1oiu.gif|left|200px]]
+
{{Seed}}
 +
[[Image:1oiu.png|left|200px]]
<!--
<!--
Line 9: Line 10:
{{STRUCTURE_1oiu| PDB=1oiu | SCENE= }}
{{STRUCTURE_1oiu| PDB=1oiu | SCENE= }}
-
'''STRUCTURE OF HUMAN THR160-PHOSPHO CDK2/CYCLIN A COMPLEXED WITH A 6-CYCLOHEXYLMETHYLOXY-2-ANILINO-PURINE INHIBITOR'''
+
===STRUCTURE OF HUMAN THR160-PHOSPHO CDK2/CYCLIN A COMPLEXED WITH A 6-CYCLOHEXYLMETHYLOXY-2-ANILINO-PURINE INHIBITOR===
-
==Overview==
+
<!--
-
The adenosine 5'-triphosphate (ATP) competitive cyclin-dependent kinase inhibitor O(6)-cyclohexylmethylguanine (NU2058, 1) has been employed as the lead in a structure-based drug discovery program resulting in the discovery of the potent CDK1 and -2 inhibitor NU6102 (3, IC(50) = 9.5 nM and 5.4 nM vs CDK1/cyclinB and CDK2/cyclinA3, respectively). The SAR for this series have been explored further by the synthesis and evaluation of 45 N(2)-substituted analogues of NU2058. These studies have confirmed the requirement for the hydrogen bonding N(2)-NH group and the requirement for an aromatic N(2)-substituent to confer potency in the series. Additional potency is conferred by the presence of a group capable of donating a hydrogen bond at the 4'-position, for example, the 4'-hydroxy derivative (25, IC(50) = 94 nM and 69 nM vs CDK1/cyclinB and CDK2/cyclinA3, respectively), 4'-monomethylsulfonamide derivative (28, IC(50) = 9 nM and 7.0 nM vs CDK1/cyclinB and CDK2/cyclinA3, respectively), and 4'-carboxamide derivative (34, IC(50) = 67 nM and 64 nM vs CDK1/cyclinB and CDK2/cyclinA3, respectively). X-ray crystal structures have been obtained for key compounds and have been used to explain the observed trends in activity.
+
The line below this paragraph, {{ABSTRACT_PUBMED_15239650}}, adds the Publication Abstract to the page
 +
(as it appears on PubMed at http://www.pubmed.gov), where 15239650 is the PubMed ID number.
 +
-->
 +
{{ABSTRACT_PUBMED_15239650}}
==About this Structure==
==About this Structure==
Line 34: Line 38:
[[Category: Serine/threonine-protein kinase]]
[[Category: Serine/threonine-protein kinase]]
[[Category: Transferase]]
[[Category: Transferase]]
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 03:54:12 2008''
+
 
 +
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 13:13:23 2008''

Revision as of 10:13, 27 July 2008

Image:1oiu.png

Template:STRUCTURE 1oiu

STRUCTURE OF HUMAN THR160-PHOSPHO CDK2/CYCLIN A COMPLEXED WITH A 6-CYCLOHEXYLMETHYLOXY-2-ANILINO-PURINE INHIBITOR

Template:ABSTRACT PUBMED 15239650

About this Structure

1OIU is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

Reference

N2-substituted O6-cyclohexylmethylguanine derivatives: potent inhibitors of cyclin-dependent kinases 1 and 2., Hardcastle IR, Arris CE, Bentley J, Boyle FT, Chen Y, Curtin NJ, Endicott JA, Gibson AE, Golding BT, Griffin RJ, Jewsbury P, Menyerol J, Mesguiche V, Newell DR, Noble ME, Pratt DJ, Wang LZ, Whitfield HJ, J Med Chem. 2004 Jul 15;47(15):3710-22. PMID:15239650

Page seeded by OCA on Sun Jul 27 13:13:23 2008

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1oiu"
Personal tools