scholarly journals Discovery of Novel Small-Molecule Inhibitors of BRD4 Using Structure-Based Virtual Screening

2013 ◽  
Vol 56 (20) ◽  
pp. 8073-8088 ◽  
Author(s):  
Lewis R. Vidler ◽  
Panagis Filippakopoulos ◽  
Oleg Fedorov ◽  
Sarah Picaud ◽  
Sarah Martin ◽  
...  
Keyword(s):  
Virtual Screening ◽  
Small Molecule ◽  
Small Molecule Inhibitors

Discovery of Novel Small Molecule Inhibitors of Dengue Viral NS2B-NS3 Protease Using Virtual Screening and Scaffold Hopping

2012 ◽  
Vol 55 (14) ◽  
pp. 6278-6293 ◽  
Author(s):  
Jing Deng ◽  
Ning Li ◽  
Hongchuan Liu ◽  
Zhili Zuo ◽  
Oi Wah Liew ◽  
...  
Keyword(s):  
Virtual Screening ◽  
Small Molecule ◽  
Small Molecule Inhibitors ◽  
Scaffold Hopping ◽  
Ns3 Protease

scholarly journals PD-1-Targeted Discovery of Peptide Inhibitors by Virtual Screening, Molecular Dynamics Simulation, and Surface Plasmon Resonance

Molecules ◽  
2019 ◽  
Vol 24 (20) ◽  
pp. 3784 ◽  
Author(s):  
Yuanqiang Wang ◽  
Haiqiong Guo ◽  
Zhiwei Feng ◽  
Siyi Wang ◽  
Yuxuan Wang ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Cell Death ◽  
Surface Plasmon Resonance ◽  
Virtual Screening ◽  
Programmed Cell Death ◽  
Surface Plasmon ◽  
Small Molecule ◽  
Plasmon Resonance ◽  
Small Molecule Inhibitors ◽  
Dynamics Simulation

The blockade of the programmed cell death protein 1/programmed cell death ligand 1 (PD-1/PD-L1) pathway plays a critical role in cancer immunotherapy by reducing the immune escape. Five monoclonal antibodies that antagonized PD-1/PD-L1 interaction have been approved by the Food and Drug Administration (FDA) and marketed as immunotherapy for cancer treatment. However, some weaknesses of antibodies, such as high cost, low stability, poor amenability for oral administration, and immunogenicity, should not be overlooked. To overcome these disadvantages, small-molecule inhibitors targeting PD-L1 were developed. In the present work, we applied in silico and in vitro approaches to develop short peptides targeting PD-1 as chemical probes for the inhibition of PD-1–PD-L1 interaction. We first predicted the potential binding pocket on PD-1/PD-L1 protein–protein interface (PPI). Sequentially, we carried out virtual screening against our in-house peptide library to identify potential ligands. WANG-003, WANG-004, and WANG-005, three of our in-house peptides, were predicted to bind to PD-1 with promising docking scores. Next, we conducted molecular docking and molecular dynamics (MD) simulation for the further analysis of interactions between our peptides and PD-1. Finally, we evaluated the affinity between peptides and PD-1 by surface plasmon resonance (SPR) binding technology. The present study provides a new perspective for the development of PD-1 inhibitors that disrupt PD-1–PD-L1 interactions. These promising peptides have the potential to be utilized as a novel chemical probe for further studies, as well as providing a foundation for further designs of potent small-molecule inhibitors targeting PD-1.

Discovery of potent small molecule inhibitors of DYRK1A by structure-based virtual screening and bioassay

2012 ◽  
Vol 22 (1) ◽  
pp. 168-171 ◽  
Author(s):  
Di Wang ◽  
Fei Wang ◽  
Yexiong Tan ◽  
Liwei Dong ◽  
Lei Chen ◽  
...  
Keyword(s):  
Virtual Screening ◽  
Small Molecule ◽  
Small Molecule Inhibitors

Discovery of small molecule inhibitors targeting the SUMO–SIM interaction using a protein interface consensus approach

MedChemComm ◽  
2014 ◽  
Vol 5 (6) ◽  
pp. 783-786 ◽  
Author(s):  
Arnout R. D. Voet ◽  
Akihiro Ito ◽  
Mikako Hirohama ◽  
Seiji Matsuoka ◽  
Naoya Tochio ◽  
...  
Keyword(s):  
Virtual Screening ◽  
Small Molecule ◽  
Protein Interactions ◽  
Small Molecule Inhibitors ◽  
Protein Interface ◽  
Consensus Approach ◽  
Screening Approach ◽  
Peptidic Inhibitors ◽  
Virtual Screening Approach

We present a virtual screening approach incorporating the consensus of protein interactions that led to the discovery of non-peptidic inhibitors.

First identification of small-molecule inhibitors of Pontin by combining virtual screening and enzymatic assay

2012 ◽  
Vol 443 (2) ◽  
pp. 549-559 ◽  
Author(s):  
Judith Elkaim ◽  
Michel Castroviejo ◽  
Driss Bennani ◽  
Said Taouji ◽  
Nathalie Allain ◽  
...  
Keyword(s):  
Virtual Screening ◽  
Small Molecule ◽  
Tumour Cell ◽  
Small Molecule Inhibitors ◽  
Colorimetric Assay ◽  
Three Dimensional ◽  
Dimensional Structure ◽  
Atp Binding Site ◽  
Set Up

The human protein Pontin, which belongs to the AAA+ (ATPases associated with various cellular activities) family, is overexpressed in several cancers and its silencing in vitro leads to tumour cell growth arrest and apoptosis, making it a good target for cancer therapy. In particular, high levels of expression were found in hepatic tumours for which the therapeutic arsenal is rather limited. The three-dimensional structure of Pontin has been resolved previously, revealing a hexameric assembly with one ADP molecule co-crystallized in each subunit. Using Vina, DrugScore and Xscore, structure-based virtual screening of 2200 commercial molecules was conducted into the ATP-binding site formed by a dimer of Pontin in order to prioritize the best candidates. Complementary to the in silico screening, a versatile and sensitive colorimetric assay was set up to measure the disruption of the ATPase activity of Pontin. This assay allowed the determination of inhibition curves for more than 20 top-scoring compounds, resulting in the identification of four ligands presenting an inhibition constant in the micromolar concentration range. Three of them inhibited tumour cell proliferation. The association of virtual screening and experimental assay thus proved successful for the discovery of the first small-molecule inhibitors of Pontin.

Virtual Screening with a Structure-Based Pharmacophore Model to Identify Small-Molecule Inhibitors of CARM1

2019 ◽  
Vol 59 (1) ◽  
pp. 522-534 ◽  
Author(s):  
Ting Ran ◽  
Wenjuan Li ◽  
Bingling Peng ◽  
Binglan Xie ◽  
Tao Lu ◽  
...  
Keyword(s):  
Virtual Screening ◽  
Small Molecule ◽  
Small Molecule Inhibitors ◽  
Pharmacophore Model

scholarly journals Discovery of small-molecule inhibitors targeting the ribosomal peptidyl transferase center (PTC) of M. tuberculosis

2019 ◽  
Vol 10 (38) ◽  
pp. 8764-8767
Author(s):  
Benjamin Tam ◽  
Dror Sherf ◽  
Shira Cohen ◽  
Sarah Adi Eisdorfer ◽  
Moshe Perez ◽  
...  
Keyword(s):  
Virtual Screening ◽  
Small Molecule ◽  
Small Molecule Inhibitors ◽  
Cost Effective ◽  
Peptidyl Transferase ◽  
Peptidyl Transferase Center ◽  
Target Rna ◽  
Effective Design

A fast, accurate, and cost-effective design of small-molecule inhibitors that target RNA using a combined NMR-fragment-based and virtual screening.

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