In Silico Investigation of the Neurotensin Receptor 1 Binding Site: Overlapping Binding Modes for Small Molecule Antagonists and the Endogenous Peptide Agonist

2015 ◽  
Vol 35 (1) ◽  
pp. 19-24 ◽  
Author(s):  
Michael Lückmann ◽  
Birgitte Holst ◽  
Thue W. Schwartz ◽  
Thomas M. Frimurer
Keyword(s):  
Binding Site ◽  
Small Molecule ◽  
In Silico ◽  
Binding Modes ◽  
Neurotensin Receptor ◽  
Endogenous Peptide ◽  
Neurotensin Receptor 1 ◽  
Peptide Agonist

scholarly journals Identification of Residues Involved in Neurotensin Binding and Modeling of the Agonist Binding Site in Neurotensin Receptor 1

2000 ◽  
Vol 275 (1) ◽  
pp. 328-336 ◽  
Author(s):  
Séverine Barroso ◽  
Françoise Richard ◽  
Delphine Nicolas-Ethève ◽  
Jean-Louis Reversat ◽  
Jean-Marie Bernassau ◽  
...  
Keyword(s):  
Binding Site ◽  
Agonist Binding ◽  
Neurotensin Receptor ◽  
Neurotensin Receptor 1

scholarly journals SPR-based fragment screening with neurotensin receptor 1 generates novel small molecule ligands

PLoS ONE ◽  
2017 ◽  
Vol 12 (5) ◽  
pp. e0175842 ◽  
Author(s):  
Sylwia Huber ◽  
Fabio Casagrande ◽  
Melanie N. Hug ◽  
Lisha Wang ◽  
Philipp Heine ◽  
...  
Keyword(s):  
Small Molecule ◽  
Fragment Screening ◽  
Neurotensin Receptor ◽  
Small Molecule Ligands ◽  
Neurotensin Receptor 1

Inhibitor Binding Sites in the Protein Tyrosine Phosphatase SHP-2

2020 ◽  
Vol 20 (11) ◽  
pp. 1017-1030
Author(s):  
Haonan Zhang ◽  
Zhengquan Gao ◽  
Chunxiao Meng ◽  
Xiangqian Li ◽  
Dayong Shi
Keyword(s):  
Small Molecule ◽  
Protein Tyrosine Phosphatase ◽  
Binding Sites ◽  
Drug Target ◽  
Tyrosine Phosphatase ◽  
Cancer Drug ◽  
Cellular Activity ◽  
Binding Modes ◽  
Inhibitor Binding ◽  
Protein Tyrosine

Protein tyrosine phosphatase 2 (SHP-2) has long been proposed as a cancer drug target. Several small-molecule compounds with different mechanisms of SHP-2 inhibition have been reported, but none are commercially available. Pool selectivity over protein tyrosine phosphatase 1 (SHP-1) and a lack of cellular activity have hindered the development of selective SHP-2 inhibitors. In this review, we describe the binding modes of existing inhibitors and SHP-2 binding sites, summarize the characteristics of the sites involved in selectivity, and identify the suitable groups for interaction with the binding sites.

Binding Modes of Small‐Molecule Inhibitors to the EED Pocket of PRC2

ChemPhysChem ◽  
2020 ◽  
Vol 21 (3) ◽  
pp. 263-271 ◽  
Author(s):  
Dading Huang ◽  
Shuaizhen Tian ◽  
Yifei Qi ◽  
John Z. H. Zhang
Keyword(s):  
Small Molecule ◽  
Small Molecule Inhibitors ◽  
Binding Modes

scholarly journals Modifications on the Tetrahydroquinoline Scaffold Targeting a Phenylalanine Cluster on GPER as Antiproliferative Compounds against Renal, Liver and Pancreatic Cancer Cells

2021 ◽  
Vol 14 (1) ◽  
pp. 49
Author(s):  
David Méndez-Luna ◽  
Loreley Araceli Morelos-Garnica ◽  
Juan Benjamín García-Vázquez ◽  
Martiniano Bello ◽  
Itzia Irene Padilla-Martínez ◽  
...  
Keyword(s):  
Binding Site ◽  
Cell Lines ◽  
Cancer Cell ◽  
Inhibitory Activity ◽  
In Silico ◽  
Cancer Cell Lines ◽  
Pancreatic Cancer Cells ◽  
Growth Inhibitory ◽  
Growth Inhibitory Activity ◽  
New Compounds

The implementation of chemo- and bioinformatics tools is a crucial step in the design of structure-based drugs, enabling the identification of more specific and effective molecules against cancer without side effects. In this study, three new compounds were designed and synthesized with suitable absorption, distribution, metabolism, excretion and toxicity (ADME-tox) properties and high affinity for the G protein-coupled estrogen receptor (GPER) binding site by in silico methods, which correlated with the growth inhibitory activity tested in a cluster of cancer cell lines. Docking and molecular dynamics (MD) simulations accompanied by a molecular mechanics/generalized Born surface area (MMGBSA) approach yielded the binding modes and energetic features of the proposed compounds on GPER. These in silico studies showed that the compounds reached the GPER binding site, establishing interactions with a phenylalanine cluster (F206, F208 and F278) required for GPER molecular recognition of its agonist and antagonist ligands. Finally, a 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyltetrazolium bromide (MTT) assay showed growth inhibitory activity of compounds 4, 5 and 7 in three different cancer cell lines—MIA Paca-2, RCC4-VA and Hep G2—at micromolar concentrations. These new molecules with specific chemical modifications of the GPER pharmacophore open up the possibility of generating new compounds capable of reaching the GPER binding site with potential growth inhibitory activities against nonconventional GPER cell models.

In silico identification of novel small molecule umami peptide from ovotransferrin

2021 ◽  
Author(s):  
Wenzhu Zhao ◽  
Jingbo He ◽  
Zhipeng Yu ◽  
Sijia Wu ◽  
Jianrong Li ◽  
...  
Keyword(s):  
Small Molecule ◽  
In Silico ◽  
In Silico Identification

Synthesis, investigation of biological effects and in silico studies of new benzimidazole derivatives as aromatase inhibitors

2020 ◽  
Vol 75 (9-10) ◽  
pp. 353-362
Author(s):  
Begüm Nurpelin Sağlık ◽  
Ahmet Mücahit Şen ◽  
Asaf Evrim Evren ◽  
Ulviye Acar Çevik ◽  
Derya Osmaniye ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
In Silico ◽  
Biological Effects ◽  
Docking Studies ◽  
Benzimidazole Derivatives ◽  
Binding Modes ◽  
Reference Drug ◽  
In Silico Studies ◽  
New Compounds ◽  
Mcf 7

AbstractInhibition of aromatase enzymes is very important in the prevention of estrogen-related diseases and the regulation of estrogen levels. Aromatase enzyme is involved in the final stage of the biosynthesis of estrogen, in the conversion of androgens to estrogen. The development of new compounds for the inhibition of aromatase enzymes is an important area for medicinal chemists in this respect. In the present study, new benzimidazole derivatives have been designed and synthesized which have reported anticancer activity in the literature. Their anticancer activity was evaluated against human A549 and MCF-7 cell lines by MTT assay. In the series, concerning MCF-7 cell line, the most potent compounds were the 4-benzylpiperidine derivatives 2c, 2g, and 2k with IC50 values of 0.032 ± 0.001, 0.024 ± 0.001, and 0.035 ± 0.001 µM, respectively, compared to the reference drug cisplatin (IC50 = 0.021 ± 0.001 µM). Then, these compounds were subject to further in silico aromatase enzyme inhibition assays to determine the possible binding modes and interactions underlying their activity. Thanks to molecular docking studies, the effectiveness of these compounds against aromatase enzyme could be simulated. Consequently, it has been found that these compounds can be settled very properly to the active site of the aromatase enzyme.

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