Identification of novel protein kinase CK1 delta (CK1δ) inhibitors through structure-based virtual screening

被引：45

作者：

Cozza, Giorgio ^{[1
,2
]}

Gianoncelli, Alessandra ^{[1
,2
]}

Montopoli, Monica ^{[3
]}

Caparrotta, Laura ^{[3
]}

Venerando, Andrea ^{[2
]}

Meggio, Flavio ^{[2
]}

Pinna, Lorenzo A. ^{[2
]}

Zagotto, Giuseppe ^{[1
]}

Moro, Stefano ^{[1
]}

机构：

[1] Univ Padua, Dipartimento Sci Farmaceut, Mol Modeling Sect, I-35131 Padua, Italy

[2] Univ Padua, Dipartimento Chim Biol, I-35121 Padua, Italy

[3] Univ Padua, Dipartimento Farmacol & Anestiol, I-35100 Padua, Italy

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2008年 / 18卷 / 20期

关键词：

protein kinase CK1 delta; kinase inhibitors; structure-based virtual screening; molecular docking;

D O I：

10.1016/j.bmcl.2008.08.072

中图分类号：

R914 [药物化学];

学科分类号：

100701 [药物化学];

摘要：

In eukaryotes, protein phosphorylation of serine, threonine or tyrosine residues by protein kinases plays an important role in many cellular processes. Members of the protein kinase CK1 family usually phosphorylate residues of serine that are close to other phosphoserine in a consensus motif of pS-X-X-S, and they are implicated in the regulation of a variety of physiological processes as well as in pathologies like cancer and Alzheimer's disease. Using a structure-based virtual screening (SBVS) approach we have identified two anthraquinones as novel CK1 delta inhibitors. These amino-anthraquinone analogs (derivatives 1 and 2) are among the most potent and selective CK1 delta inhibitors known today (IC50 = 0.3 and 0.6 mu M, respectively). (C) 2008 Elsevier Ltd. All rights reserved.

引用

页码：5672 / 5675

页数：4

共 28 条

[1]

Inhibitors of casein kinase 1 block the growth of Leishmania major promastigotes in vitro [J].