4ACM

CDK2 IN COMPLEX WITH 3-AMINO-6-(4-{[2-(DIMETHYLAMINO)ETHYL]SULFAMOYL}-PHENYL)-N-PYRIDIN-3-YLPYRAZINE-2-CARBOXAMIDE

4ACM の概要

• エントリーDOI: 10.2210/pdb4acm/pdb
• 関連するPDBエントリー: 1AQ1 1B38 1B39 1BUH 1CKP 1DI8 1DM2 1E1V 1E1X 1E9H 1F5Q 1FIN 1FQ1 1FVT 1FVV 1G5S 1GIH 1GII 1GIJ 1GY3 1GZ8 1H00 1H01 1H07 1H08 1H0V 1H0W 1H1P 1H1Q 1H1R 1H1S 1H24 1H25 1H26 1H27 1H28 1HCK 1HCL 1JST 1JSU 1JSV 1JVP 1KE5 1KE6 1KE7 1KE8 1KE9 1OGU 1OI9 1OIQ 1OIR 1OIT 1OIU 1OIY 1OKV 1OKW 1OL1 1OL2 1P2A 1P5E 1PF8 1PKD 1PW2 1PXI 1PXJ 1PXK 1PXL 1PXM 1PXN 1PXO 1PXP 1PYE 1QMZ 1R78 1URC 1URW 1V1K 1VYW 1VYZ 1W0X 1W8C 1W98 1WCC 1Y8Y 1Y91 1YKR 2A0C 2A4L 2B52 2B53 2B54 2B55 2BHE 2BHH 2BKZ 2BPM 2BTR 2BTS 2C4G 2C5N 2C5O 2C5V 2C5X 2C5Y 2C68 2C69 2C6I 2C6K 2C6L 2C6M 2C6O 2C6T 2CCH 2CCI 2CJM 2CLX 2EXM 2G9X 2IW6 2IW8 2IW9 2J9M 2JGZ 2UUE 2UZB 2UZD 2UZE 2UZL 2UZN 2UZO 2V0D 2V22 2VTA 2VTH 2VTI 2VTJ 2VTL 2VTM 2VTN 2VTO 2VTP 2VTQ 2VTR 2VTS 2VTT 2VU3 2VV9 2W05 2W06 2W17 2W1H 2WEV 2WFY 2WHB 2WIH 2WIP 2WMA 2WMB 2WPA 2WXV 2X1N 2XMY 2XNB
• 分子名称: CYCLIN-DEPENDENT KINASE 2, GLYCEROL, 3-AMINO-6-(4-{[2-(DIMETHYLAMINO)ETHYL]SULFAMOYL}PHENYL)-N-PYRIDIN-3-YLPYRAZINE-2-CARBOXAMIDE, ... (4 entities in total)
• 機能のキーワード: mitosis, cell cycle, transferase, serine/threonine- protein kinase, atp-binding, cell division, nucleotide-binding
• 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: 34628.22

構造登録者

Berg, S.,Bhat, R.,Anderson, M.,Bergh, M.,Brassington, C.,Hellberg, S.,Jerning, E.,Hogdin, K.,Lo-Alfredsson, Y.,Neelissen, J.,Nilsson, Y.,Ormo, M.,Soderman, P.,Stanway, J.,Tucker, J.,von Berg, S.,Weigelt, T.,Xue, Y. (登録日: 2011-12-16, 公開日: 2012-05-16, 最終更新日: 2024-05-01)

主引用文献

Berg, S.,Bergh, M.,Hellberg, S.,Hogdin, K.,Lo-Alfredsson, Y.,Soderman, P.,von Berg, S.,Weigelt, T.,Ormo, M.,Xue, Y.,Tucker, J.,Neelissen, J.,Jerning, E.,Nilsson, Y.,Bhat, R.
Discovery of novel potent and highly selective glycogen synthase kinase-3 beta (GSK3 beta ) inhibitors for Alzheimer's disease: design, synthesis, and characterization of pyrazines.
J. Med. Chem., 55:9107-9119, 2012

PubMed Abstract: Glycogen synthase kinase-3β, also called tau phosphorylating kinase, is a proline-directed serine/threonine kinase which was originally identified due to its role in glycogen metabolism. Active forms of GSK3β localize to pretangle pathology including dystrophic neuritis and neurofibrillary tangles in Alzheimer's disease (AD) brain. By using a high throughput screening (HTS) approach to search for new chemical series and cocrystallization of key analogues to guide the optimization and synthesis of our pyrazine series, we have developed highly potent and selective inhibitors showing cellular efficacy and blood-brain barrier penetrance. The inhibitors are suitable for in vivo efficacy testing and may serve as a new treatment strategy for Alzheimer's disease.

PubMed: 22489897
DOI: 10.1021/jm201724m

実験手法

X-RAY DIFFRACTION (1.63 Å)