scholarly journals Ligand-based pharmacophore modeling, virtual screening and biological evaluation to identify novel TGR5 agonists

RSC Advances ◽  
2021 ◽  
Vol 11 (16) ◽  
pp. 9403-9409
Author(s):  
Shizhen Zhao ◽  
Xinping Li ◽  
Wenjing Peng ◽  
Le Wang ◽  
Wenling Ye ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Virtual Screening ◽  
Pharmacophore Modeling ◽  
Biological Evaluation ◽  
Pharmacophore Mapping

The ligand-based virtual screening combined with pharmacophore mapping and molecular docking was performed to identify novel nonsteroidal TGR5 agonists.

scholarly journals Structure-Based Pharmacophore Modeling, Virtual Screening, Molecular Docking and Biological Evaluation for Identification of Potential Poly (ADP-Ribose) Polymerase-1 (PARP-1) Inhibitors

Molecules ◽  
2019 ◽  
Vol 24 (23) ◽  
pp. 4258 ◽  
Author(s):  
Yunjiang Zhou ◽  
Shi Tang ◽  
Tingting Chen ◽  
Miao-Miao Niu
Keyword(s):  
Molecular Docking ◽  
Virtual Screening ◽  
A549 Cells ◽  
Pharmacophore Modeling ◽  
Biological Evaluation ◽  
Human Lung Cancer ◽  
Dependent Manner ◽  
Biological Processes ◽  
Dose Dependent ◽  
Parp 1

Poly (ADP-ribose) polymerase-1 (PARP-1) plays critical roles in many biological processes and is considered as a potential target for anticancer therapy. Although some PARP-1 inhibitors have been reported, their clinical application in cancer therapy is limited by some shortcomings such as weak affinity, low selectivity and adverse side effects. To identify highly potent and selective PARP-1 inhibitors, an integrated protocol that combines pharmacophore mapping, virtual screening and molecular docking was constructed. It was then used as a screening query to identify potent leads with unknown scaffolds from an in-house database. Finally, four retrieved compounds were selected for biological evaluation. Biological testing indicated that the four compounds showed strong inhibitory activities on the PARP-1 (IC50 < 0.2 μM). MTT assay confirmed that compounds 1–4 inhibited the growth of human lung cancer A549 cells in a dose-dependent manner. The obtained compounds from this study may be potential leads for PARP-1 inhibition in the treatment of cancer.

scholarly journals Pharmacophore modeling and virtual screening studies for discovery of novel farnesoid X receptor (FXR) agonists

RSC Advances ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 2158-2166
Author(s):  
Shizhen Zhao ◽  
Wenjing Peng ◽  
Xinping Li ◽  
Le Wang ◽  
Wenbo Yin ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Virtual Screening ◽  
Pharmacophore Modeling ◽  
Farnesoid X Receptor ◽  
Pharmacophore Mapping

In this study, we have employed an integrated virtual screening by combining ligand-based pharmacophore mapping and molecular docking to identify novel nonsteroidal FXR agonists.

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

Molecules ◽  
2019 ◽  
Vol 25 (1) ◽  
pp. 107 ◽  
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.

Sign in / Sign up

Export Citation Format

Share Document