pmid: 31760818,   nlmid 101150203,  doi:10.1080/14756366.2019.1693702

Identification of novel CDK2 inhibitors by a multistage virtual screening method based on SVM, pharmacophore and docking model.


Liang, Jing-Wei Wang, Ming-Yang Wang, Shan Li, Shi-Long Li, Wan-Qiu Meng, Fan-Hao

Vol. 35, Issue 35, Dec.2020

Journal of enzyme inhibition and medicinal chemistry (J Enzyme Inhib Med Chem),  ISSN 1475-6374

Abstract

Cyclin-dependent kinase 2 (CDK2) is the family of Ser/Thr protein kinases that has emerged as a highly selective with low toxic cancer therapy target. A multistage virtual screening method combined by SVM, protein-ligand interaction fingerprints (PLIF) pharmacophore and docking was utilised for screening the CDK2 inhibitors. The evaluation of the validation set indicated that this method can be used to screen large chemical databases because it has a high hit-rate and enrichment factor (80.1% and 332.83 respectively). Six compounds were screened out from NCI, Enamine and Pubchem database. After molecular dynamics and binding free energy calculation, two compounds had great potential as novel CDK2 inhibitors and they also showed selective inhibition against CDK2 in the kinase activity assay.


MESH Headings

A549 Cells | Antineoplastic Agents | Cell Proliferation | Cyclin-Dependent Kinase 2 | Dose-Response Relationship, Drug | Drug Evaluation, Preclinical | Drug Screening Assays, Antitumor | HCT116 Cells | Humans | Molecular Docking Simulation | Molecular Structure | Protein Kinase Inhibitors | Structure-Activity Relationship | Support Vector Machine | analysis | chemistry | pharmacology | drug effects | antagonists & inhibitors | metabolism | analysis | chemistry | pharmacology |


Article Keywords

CDK2 | SVM | Virtual screening | docking | molecular dynamics |


Chemical

Antineoplastic Agents | Protein Kinase Inhibitors | CDK2 protein, human | Cyclin-Dependent Kinase 2 |

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