3IGG

Novel CDK-5 inhibitors - crystal structure of inhibitor EFQ with CDK-2

3IGG の概要

• エントリーDOI: 10.2210/pdb3igg/pdb
• 関連するPDBエントリー: 3IG7
• 分子名称: Cell division protein kinase 2, N-[1-(cis-3-hydroxycyclobutyl)-1H-imidazol-4-yl]-2-(4-methoxyphenyl)acetamide (3 entities in total)
• 機能のキーワード: protein kinase, transferase, serine/threonine protein kinase, inhibitor, atp-binding, cell cycle, cell division, kinase, mitosis, nucleotide-binding, phosphoprotein, polymorphism, serine/threonine-protein kinase
• 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: 34303.87

構造登録者

Pandit, J. (登録日: 2009-07-27, 公開日: 2009-09-08, 最終更新日: 2024-11-27)

主引用文献

Helal, C.J.,Kang, Z.,Lucas, J.C.,Gant, T.,Ahlijanian, M.K.,Schachter, J.B.,Richter, K.E.,Cook, J.M.,Menniti, F.S.,Kelly, K.,Mente, S.,Pandit, J.,Hosea, N.
Potent and cellularly active 4-aminoimidazole inhibitors of cyclin-dependent kinase 5/p25 for the treatment of Alzheimer's disease.
Bioorg.Med.Chem.Lett., 19:5703-5707, 2009

PubMed Abstract: Utilizing structure-based drug design, a 4-aminoimidazole heterocyclic core was synthesized as a replacement for a 2-aminothiazole due to potential metabolically mediated toxicity. The synthetic route utilized allowed for ready synthesis of 1-substituted-4-aminoimidazoles. SAR exploration resulted in the identification of a novel cis-substituted cyclobutyl group that gave improved enzyme and cellular potency against cdk5/p25 with up to 30-fold selectivity over cdk2/cyclin E.

PubMed: 19700321
DOI: 10.1016/j.bmcl.2009.08.019

実験手法

X-RAY DIFFRACTION (1.8 Å)