A Computational Workflow for the Identification of Novel Fragments Acting as Inhibitors of the Activity of Protein Kinase CK1δ

被引：17

作者：

Bolcato, Giovanni ^{[1
]}

Cescon, Eleonora ^{[2
]}

Pavan, Matteo ^{[1
]}

Bissaro, Maicol ^{[1
]}

Bassani, Davide ^{[1
]}

Federico, Stephanie ^{[2
]}

Spalluto, Giampiero ^{[2
]}

Sturlese, Mattia ^{[1
]}

Moro, Stefano ^{[1
]}

机构：

[1] Univ Padua, Dept Pharmaceut & Pharmacol Sci, Mol Modeling Sect MMS, Via Marzolo 5, I-35131 Padua, Italy

[2] Univ Trieste, Dept Chem & Pharmaceut Sci, Via Licio Giorgeri 1, I-34127 Trieste, Italy

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2021年 / 22卷 / 18期

关键词：

fragment-based drug discovery; molecular docking; molecular dynamics; supervised molecular dynamics; protein kinase CK1 delta; MOLECULAR-DYNAMICS SUMD; CASEIN KINASE-1; LIGAND DOCKING; DELTA; BINDING; PHOSPHORYLATION; CK1; PROGRAM; ACCUMULATION; SIMULATIONS;

D O I：

10.3390/ijms22189741

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Fragment-Based Drug Discovery (FBDD) has become, in recent years, a consolidated approach in the drug discovery process, leading to several drug candidates under investigation in clinical trials and some approved drugs. Among these successful applications of the FBDD approach, kinases represent a class of targets where this strategy has demonstrated its real potential with the approved kinase inhibitor Vemurafenib. In the Kinase family, protein kinase CK1 isoform delta (CK1 delta) has become a promising target in the treatment of different neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. In the present work, we set up and applied a computational workflow for the identification of putative fragment binders in large virtual databases. To validate the method, the selected compounds were tested in vitro to assess the CK1 delta inhibition.

引用

页数：13

共 62 条

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