2B55

Human cyclin dependent kinase 2 (cdk2) complexed with indenopyraxole DIN-101312

2B55 の概要

• エントリーDOI: 10.2210/pdb2b55/pdb
• 関連するPDBエントリー: 2B52 2B53 2B54
• 分子名称: Cell division protein kinase 2, 2-(4-(AMINOMETHYL)PIPERIDIN-1-YL)-N-(3_CYCLOHEXYL-4-OXO-2,4-DIHYDROINDENO[1,2-C]PYRAZOL-5-YL)ACETAMIDE (3 entities in total)
• 機能のキーワード: protein kinase, cell cycle, phosphorylation, cell division, mitosis, inhibition, transferase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 34398.02

構造登録者

Muckelbauer, J. (登録日: 2005-09-27, 公開日: 2005-10-11, 最終更新日: 2024-02-14)

主引用文献

Yue, E.W.,Higley, C.A.,Dimeo, S.V.,Carini, D.J.,Nugiel, D.A.,Benware, C.,Benfield, P.A.,Cox, S.,Burton, C.R.,Grafstrom, R.H.,Sharp, D.M.,Sisk, L.M.,Boylan, J.F.,Muckelbauer, J.K.,Smallwood, A.M.,Chen, H.,Chang, C.-H.,Seitz, S.P.,Trainor, G.L.
Synthesis and Evaluation of Indenopyrazoles as Cyclin-Dependent Kinase Inhibitors. 3. Structure Activity Relationships at C3
J.Med.Chem., 45:5233-5248, 2002

PubMed Abstract: The identification of indeno[1,2-c]pyrazol-4-ones as inhibitors of cyclin-dependent kinases (CDKs) has led to the discovery of a series of novel and potent compounds. Herein, we report the effects of substitutions at C3 of the indeno[1,2-c]pyrazol-4-one core with alkyls, heterocycles, and substituted phenyls. Substitutions at the para position of the phenyl ring at C3 were generally well-tolerated; however, larger groups were generally inactive. For alkyls directly attached to C3, longer chain substituents were not tolerated; however, shorter alkyl groups and cyclic alkyls were acceptable. In general, the heterocycles at C3 gave the most potent analogues. One such heterocycle, 24j, was examined in detail and was determined to have a biological profile consistent with CDK inhibition. An X-ray crystal structure of one of the alkyl compounds, 13q, complexed with CDK2 was determined and showed the inhibitor residing in the adenosine 5'-triphosphate pocket of the enzyme.

PubMed: 12431051
DOI: 10.1021/jm0201722

実験手法

X-RAY DIFFRACTION (1.85 Å)