1ogu: Difference between revisions

Revision as of 15:17, 21 February 2008

STRUCTURE OF HUMAN THR160-PHOSPHO CDK2/CYCLIN A COMPLEXED WITH A 2-ARYLAMINO-4-CYCLOHEXYLMETHYL-5-NITROSO-6-AMINOPYRIMIDINE INHIBITOR

OverviewOverview

A series of O(4)-cyclohexylmethyl-5-nitroso-6-aminopyrimidines bearing 2-arylamino substituents was synthesised and evaluated for CDK1 and CDK2 inhibitory activity. Consistent with analogous studies with O(6)-cyclohexylmethylpurines, 2-arylaminopyrimidines with a sulfonamide or carboxamide group at the 4'-position were potent inhibitors, with IC(50) values against CDK2 of 1.1+/-0.3 and 34+/-8 nM, respectively. The crystal structure of the 4'-carboxamide derivative, in complex with phospho-Thr160 CDK2/cyclin A, confirmed the expected binding mode of the inhibitor, and revealed an additional interaction between the carboxamide function and an aspartate residue.

About this StructureAbout this Structure

1OGU is a Protein complex structure of sequences from Homo sapiens with and as ligands. Active as Transferred entry: 2.7.11.1, with EC number 2.7.1.37 Known structural/functional Site: . Full crystallographic information is available from OCA.

ReferenceReference

Structure-based design of 2-arylamino-4-cyclohexylmethyl-5-nitroso-6-aminopyrimidine inhibitors of cyclin-dependent kinases 1 and 2., Sayle KL, Bentley J, Boyle FT, Calvert AH, Cheng Y, Curtin NJ, Endicott JA, Golding BT, Hardcastle IR, Jewsbury P, Mesguiche V, Newell DR, Noble ME, Parsons RJ, Pratt DJ, Wang LZ, Griffin RJ, Bioorg Med Chem Lett. 2003 Sep 15;13(18):3079-82. PMID:12941338

Page seeded by OCA on Thu Feb 21 14:17:35 2008

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OCA

@@ Line 4: / Line 4: @@
 ==Overview==
-A series of O(4)-cyclohexylmethyl-5-nitroso-6-aminopyrimidines bearing, 2-arylamino substituents was synthesised and evaluated for CDK1 and CDK2, inhibitory activity. Consistent with analogous studies with, O(6)-cyclohexylmethylpurines, 2-arylaminopyrimidines with a sulfonamide or, carboxamide group at the 4'-position were potent inhibitors, with IC(50), values against CDK2 of 1.1+/-0.3 and 34+/-8 nM, respectively. The crystal, structure of the 4'-carboxamide derivative, in complex with phospho-Thr160, CDK2/cyclin A, confirmed the expected binding mode of the inhibitor, and, revealed an additional interaction between the carboxamide function and an, aspartate residue.
+A series of O(4)-cyclohexylmethyl-5-nitroso-6-aminopyrimidines bearing 2-arylamino substituents was synthesised and evaluated for CDK1 and CDK2 inhibitory activity. Consistent with analogous studies with O(6)-cyclohexylmethylpurines, 2-arylaminopyrimidines with a sulfonamide or carboxamide group at the 4'-position were potent inhibitors, with IC(50) values against CDK2 of 1.1+/-0.3 and 34+/-8 nM, respectively. The crystal structure of the 4'-carboxamide derivative, in complex with phospho-Thr160 CDK2/cyclin A, confirmed the expected binding mode of the inhibitor, and revealed an additional interaction between the carboxamide function and an aspartate residue.
 ==About this Structure==
@@ Line 13: / Line 13: @@
 [[Category: Homo sapiens]]
 [[Category: Protein complex]]
-[[Category: Transferred entry: 2.7.11.1]]
+[[Category: Transferred entry: 2 7.11 1]]
-[[Category: Endicott, J.A.]]
+[[Category: Endicott, J A.]]
-[[Category: Noble, M.E.M.]]
+[[Category: Noble, M E.M.]]
-[[Category: Pratt, D.J.]]
+[[Category: Pratt, D J.]]
 [[Category: SGM]]
 [[Category: ST8]]
@@ Line 28: / Line 28: @@
 [[Category: transferase]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Feb  3 09:57:57 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:17:35 2008''