5K4J

Crystal Structure of CDK2 in complex with compound 22

5K4J の概要

• エントリーDOI: 10.2210/pdb5k4j/pdb
• 関連するPDBエントリー: 5K4I
• 分子名称: Cyclin-dependent kinase 2, 1-[(1~{S})-1-(4-chloranyl-3-fluoranyl-phenyl)-2-oxidanyl-ethyl]-4-[2-[(2-methylpyrazol-3-yl)amino]pyrimidin-4-yl]pyridin-2-one (3 entities in total)
• 機能のキーワード: protein kinase, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 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: 34488.43

構造登録者

Yin, J.,Wang, W. (登録日: 2016-05-20, 公開日: 2016-07-06, 最終更新日: 2024-03-06)

主引用文献

Blake, J.F.,Burkard, M.,Chan, J.,Chen, H.,Chou, K.J.,Diaz, D.,Dudley, D.A.,Gaudino, J.J.,Gould, S.E.,Grina, J.,Hunsaker, T.,Liu, L.,Martinson, M.,Moreno, D.,Mueller, L.,Orr, C.,Pacheco, P.,Qin, A.,Rasor, K.,Ren, L.,Robarge, K.,Shahidi-Latham, S.,Stults, J.,Sullivan, F.,Wang, W.,Yin, J.,Zhou, A.,Belvin, M.,Merchant, M.,Moffat, J.,Schwarz, J.B.
Discovery of (S)-1-(1-(4-Chloro-3-fluorophenyl)-2-hydroxyethyl)-4-(2-((1-methyl-1H-pyrazol-5-yl)amino)pyrimidin-4-yl)pyridin-2(1H)-one (GDC-0994), an Extracellular Signal-Regulated Kinase 1/2 (ERK1/2) Inhibitor in Early Clinical Development.
J.Med.Chem., 59:5650-5660, 2016

PubMed Abstract: The extracellular signal-regulated kinases ERK1/2 represent an essential node within the RAS/RAF/MEK/ERK signaling cascade that is commonly activated by oncogenic mutations in BRAF or RAS or by upstream oncogenic signaling. While targeting upstream nodes with RAF and MEK inhibitors has proven effective clinically, resistance frequently develops through reactivation of the pathway. Simultaneous targeting of multiple nodes in the pathway, such as MEK and ERK, offers the prospect of enhanced efficacy as well as reduced potential for acquired resistance. Described herein is the discovery and characterization of GDC-0994 (22), an orally bioavailable small molecule inhibitor selective for ERK kinase activity.

PubMed: 27227380
DOI: 10.1021/acs.jmedchem.6b00389

実験手法

X-RAY DIFFRACTION (1.6 Å)