8VXE

Structure of p38 alpha (Mitogen-activated protein kinase 14) complexed with inhibitor 6

これはPDB形式変換不可エントリーです。

8VXE の概要

• エントリーDOI: 10.2210/pdb8vxe/pdb
• 分子名称: Mitogen-activated protein kinase 14, (4M)-4-[3-(4-fluorophenyl)-1-methyl-1H-pyrazol-4-yl]-1H-pyrrolo[2,3-b]pyridine (3 entities in total)
• 機能のキーワード: kinase, transferase, p38 alpha, mapk14, inhibitor, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 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: 45242.30

構造登録者

Blaesse, M.,Steinbacher, S.,Shaffer, P.L.,Sharma, S.,Thompson, A.A. (登録日: 2024-02-04, 公開日: 2024-05-08)

主引用文献

McCarver, S.,Hanna, L.,Samant, A.,Thompson, A.A.,Seierstad, M.,Saha, A.,Wu, D.,Lord, B.,Sutton, S.W.,Shah, V.,Milligan, C.M.,Wennerholm, M.,Shelton, J.,Lebold, T.P.,Shireman, B.T.
Structure-Based Optimization of Selective and Brain Penetrant CK1 delta Inhibitors for the Treatment of Circadian Disruptions.
Acs Med.Chem.Lett., 15:486-492, 2024

PubMed Abstract: Neuropsychiatric disorders such as major depressive disorders and schizophrenia are often associated with disruptions to the normal 24 h sleep wake cycle. Casein kinase 1 (CK1δ) is an integral part of the molecular machinery that regulates circadian rhythms. Starting from a cluster of bicyclic pyrazoles identified from a virtual screening effort, we utilized structure-based drug design to identify and reinforce a unique "hinge-flip" binding mode that provides a high degree of selectivity for CK1δ versus the kinome. Pharmacokinetics, brain exposure, and target engagement as measured by autoradiography are described for advanced analogs.

PubMed: 38628796
DOI: 10.1021/acsmedchemlett.3c00523

実験手法

X-RAY DIFFRACTION (1.85 Å)