Discovery of Novel NAMPT Inhibitors Based on Pharmacophore Modeling and Virtual Screening Techniques

Checkpoint kinase 2 (Chk2) has a great effect on DNA-damage and plays an important role in response to DNA double-strand breaks and related lesions. In this study, we will concentrate on Chk2 and the purpose is to find the potential inhibitors by the pharmacophore hypotheses (PhModels), combinatorial fusion, and virtual screening techniques. Applying combinatorial fusion into PhModels and virtual screening techniques is a novel design strategy for drug design. We used combinatorial fusion to analyze the prediction results and then obtained the best correlation coefficient of the testing set (rtest) with the value 0.816 by combining theBesttrainBesttestandFasttrainFasttestprediction results. The potential inhibitors were selected from NCI database by screening according toBesttrainBesttest+FasttrainFasttestprediction results and molecular docking with CDOCKER docking program. Finally, the selected compounds have high interaction energy between a ligand and a receptor. Through these approaches, 23 potential inhibitors for Chk2 are retrieved for further study.

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Design checkpoint kinase 2 inhibitors by pharmacophore modeling and virtual screening techniques

Bioorganic & Medicinal Chemistry Letters ◽

10.1016/j.bmcl.2013.09.080 ◽

2013 ◽

Vol 23 (23) ◽

pp. 6286-6291 ◽

Cited By ~ 2

Author(s):

Yen-Ling Wang ◽

Chun-Yuan Lin ◽

Kuei-Chung Shih ◽

Jui-Wen Huang ◽

Chuan-Yi Tang

Keyword(s):

Virtual Screening ◽

Pharmacophore Modeling ◽

Checkpoint Kinase ◽

Screening Techniques ◽

Checkpoint Kinase 2

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Identification of Novel Structurally Diverse Anaplastic Lymphoma Kinase Inhibitors Based on Pharmacophore Modeling, Virtual Screening and Molecular Docking

Combinatorial Chemistry & High Throughput Screening ◽

10.2174/1386207319666160801153455 ◽

2016 ◽

Vol 19 (9) ◽

pp. 691-704

Author(s):

Rong You ◽

Lu Zhou ◽

Liangliang Zhong ◽

Xiaoli Li ◽

Suwen Zhou ◽

...

Keyword(s):

Molecular Docking ◽

Virtual Screening ◽

Anaplastic Lymphoma Kinase ◽

Kinase Inhibitors ◽

Pharmacophore Modeling ◽

Anaplastic Lymphoma

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Discovery of Camptothecin Based Topoisomerase I Inhibitors: Identification Using an Atom Based 3D-QSAR, Pharmacophore Modeling, Virtual Screening and Molecular Docking Approach

Combinatorial Chemistry & High Throughput Screening ◽

10.2174/1386207319666160810154346 ◽

2016 ◽

Vol 19 (9) ◽

pp. 752-763 ◽

Cited By ~ 4

Author(s):

Sanal Dev ◽

Sunil Dhaneshwar ◽

Bijo Mathew

Keyword(s):

Molecular Docking ◽

Virtual Screening ◽

Topoisomerase I ◽

3D Qsar ◽

Pharmacophore Modeling ◽

Topoisomerase I Inhibitors ◽

Docking Approach

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Virtual Screening Techniques to Probe the Antimalarial Activity of some Traditionally Used Phytochemicals

Combinatorial Chemistry & High Throughput Screening ◽

10.2174/1386207319666160420141200 ◽

2016 ◽

Vol 19 (7) ◽

pp. 572-591 ◽

Cited By ~ 4

Author(s):

Indira G. Shibi ◽

Lilly Aswathy ◽

Radhakrishnan S. Jisha ◽

Vijay H. Masand ◽

Jayant M. Gajbhiye

Keyword(s):

Virtual Screening ◽

Antimalarial Activity ◽

Screening Techniques

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Structure-Based Virtual Screening and Biological Evaluation of Peptide Inhibitors for Polo-Box Domain

Molecules ◽

10.3390/molecules25010107 ◽

2019 ◽

Vol 25 (1) ◽

pp. 107 ◽

Cited By ~ 1

Author(s):

Fang Yan ◽

Guangmei Liu ◽

Tingting Chen ◽

Xiaochen Fu ◽

Miao-Miao Niu

Keyword(s):

Cell Cycle ◽

Virtual Screening ◽

Fold Increase ◽

Pharmacophore Modeling ◽

Biological Evaluation ◽

Peptide Inhibitors ◽

Regulatory Proteins ◽

Competitive Binding Assay ◽

M Phase ◽

Cell Cycle Regulatory Proteins

The polo-box domain of polo-like kinase 1 (PLK1-PBD) is proved to have crucial roles in cell proliferation. Designing PLK1-PBD inhibitors is challenging due to their poor cellular penetration. In this study, we applied a virtual screening workflow based on a combination of structure-based pharmacophore modeling with molecular docking screening techniques, so as to discover potent PLK1-PBD peptide inhibitors. The resulting 9 virtual screening peptides showed affinities for PLK1-PBD in a competitive binding assay. In particular, peptide 5 exhibited an approximately 100-fold increase in inhibitory activity (IC50 = 70 nM), as compared with the control poloboxtide. Moreover, cell cycle experiments indicated that peptide 5 effectively inhibited the expression of p-Cdc25C and cell cycle regulatory proteins by affecting the function of PLK1-PBD, thereby inducing mitotic arrest at the G2/M phase. Overall, peptide 5 can serve as a potent lead for further investigation as PLK1-PBD inhibitors.

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