1KE6

CYCLIN-DEPENDENT KINASE 2 (CDK2) COMPLEXED WITH N-METHYL-{4-[2-(7-OXO-6,7-DIHYDRO-8H-[1,3]THIAZOLO[5,4-E]INDOL-8-YLIDENE)HYDRAZINO]PHENYL}METHANESULFONAMIDE

1KE6 の概要

• エントリーDOI: 10.2210/pdb1ke6/pdb
• 関連するPDBエントリー: 1KE5 1KE7 1KE8 1KE9
• 分子名称: Cell division protein kinase 2, N-METHYL-{4-[2-(7-OXO-6,7-DIHYDRO-8H-[1,3]THIAZOLO[5,4-E]INDOL-8-YLIDENE)HYDRAZINO]PHENYL}METHANESULFONAMIDE (3 entities in total)
• 機能のキーワード: cyclin, kinase, transferase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm, cytoskeleton, microtubule organizing center, centrosome: P24941
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 34377.95

構造登録者

Bramson, H.N.,Corona, J.,Davis, S.T.,Dickerson, S.H.,Edelstein, M.,Frye, S.V.,Gampe, R.T.,Hassell, A.H.,Shewchuk, L.M.,Kuyper, L.F. (登録日: 2001-11-14, 公開日: 2002-05-14, 最終更新日: 2023-08-16)

主引用文献

Bramson, H.N.,Corona, J.,Davis, S.T.,Dickerson, S.H.,Edelstein, M.,Frye, S.V.,Gampe Jr., R.T.,Harris, P.A.,Hassell, A.,Holmes, W.D.,Hunter, R.N.,Lackey, K.E.,Lovejoy, B.,Luzzio, M.J.,Montana, V.,Rocque, W.J.,Rusnak, D.,Shewchuk, L.,Veal, J.M.,Walker, D.H.,Kuyper, L.F.
Oxindole-based inhibitors of cyclin-dependent kinase 2 (CDK2): design, synthesis, enzymatic activities, and X-ray crystallographic analysis.
J.Med.Chem., 44:4339-4358, 2001

PubMed Abstract: Two closely related classes of oxindole-based compounds, 1H-indole-2,3-dione 3-phenylhydrazones and 3-(anilinomethylene)-1,3-dihydro-2H-indol-2-ones, were shown to potently inhibit cyclin-dependent kinase 2 (CDK2). The initial lead compound was prepared as a homologue of the 3-benzylidene-1,3-dihydro-2H-indol-2-one class of kinase inhibitor. Crystallographic analysis of the lead compound bound to CDK2 provided the basis for analogue design. A semiautomated method of ligand docking was used to select compounds for synthesis, and a number of compounds with low nanomolar inhibitory activity versus CDK2 were identified. Enzyme binding determinants for several analogues were evaluated by X-ray crystallography. Compounds in this series inhibited CDK2 with a potency approximately 10-fold greater than that for CDK1. Members of this class of inhibitor cause an arrest of the cell cycle and have shown potential utility in the prevention of chemotherapy-induced alopecia.

PubMed: 11728181
DOI: 10.1021/jm010117d

実験手法

X-RAY DIFFRACTION (2 Å)