2hog: Difference between revisions

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==Overview==

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.

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 Structure==

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[[Category: kinase]]

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on ~~Wed Jan 23 15~~:35:03 2008''

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:44:01 2008''

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@@ Line 4: / Line 4: @@
 ==Overview==
-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.
+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 Structure==
@@ Line 21: / Line 21: @@
 [[Category: kinase]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 15:35:03 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:44:01 2008''