Combining Hit Identification Strategies: Fragment-Based and in Silico Approaches to Orally Active 2-Aminothieno[2,3-d]pyrimidine Inhibitors of the Hsp90 Molecular Chaperone

2009 ◽  
Vol 52 (15) ◽  
pp. 4794-4809 ◽  
Author(s):  
Paul A. Brough ◽  
Xavier Barril ◽  
Jenifer Borgognoni ◽  
Patrick Chene ◽  
Nicholas G. M. Davies ◽  
...  
Keyword(s):  
Molecular Chaperone ◽  
In Silico ◽  
Hit Identification ◽  
Orally Active

Discovery of an Orally Active and Long‐Acting DPP‐IV Inhibitor through Property‐Based Optimization with an in Silico Biotransformation Prediction Tool

ChemMedChem ◽  
2020 ◽  
Vol 15 (16) ◽  
pp. 1608-1617
Author(s):  
Shaogao Zeng ◽  
Wenyuan Dou ◽  
Manna Li ◽  
Yang Zhou ◽  
Jiehuang Guo ◽  
...  
Keyword(s):  
In Silico ◽  
Prediction Tool ◽  
Dpp Iv ◽  
Long Acting ◽  
Orally Active

Novel Selective Orally Active CRTH2 Antagonists for Allergic Inflammation Developed from in Silico Derived Hits

2006 ◽  
Vol 49 (23) ◽  
pp. 6638-6641 ◽  
Author(s):  
Trond Ulven ◽  
Jean-Marie Receveur ◽  
Marie Grimstrup ◽  
Øystein Rist ◽  
Thomas M. Frimurer ◽  
...  
Keyword(s):  
In Silico ◽  
Allergic Inflammation ◽  
Orally Active

scholarly journals Identification and in silico analysis of the Citrus HSP70 molecular chaperone gene family

2007 ◽  
Vol 30 (3 suppl) ◽  
pp. 881-887 ◽  
Author(s):  
Luciano G. Fietto ◽  
Maximiller D.L. Costa ◽  
Cosme D. Cruz ◽  
Alessandra A. Souza ◽  
Marcos A. Machado ◽  
...  
Keyword(s):  
Gene Family ◽  
Molecular Chaperone ◽  
In Silico ◽  
In Silico Analysis ◽  
Silico Analysis

scholarly journals Synthesis, In Vitro, In Vivo and In Silico Antidiabetic Bioassays of 4-Niztro(thio)phenoxyisobutyric Acids Acting as Unexpected PPARγ Modulators: An In Combo Study

2022 ◽  
Vol 15 (1) ◽  
pp. 102
Author(s):  
Blanca Colin-Lozano ◽  
Héctor Torres-Gomez ◽  
Sergio Hidalgo-Figueroa ◽  
Fabiola Chávez-Silva ◽  
Samuel Estrada-Soto ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Spectral Analysis ◽  
In Silico ◽  
In Vivo Studies ◽  
In Vitro Expression ◽  
Modes Of Action ◽  
In Vivo Effects ◽  
Orally Active

Four isobutyric acids (two nitro and two acetamido derivatives) were prepared in two steps and characterized using spectral analysis. The mRNA concentrations of PPARγ and GLUT-4 (two proteins documented as key diabetes targets) were increased by 3T3-L1 adipocytes treated with compounds 1–4, but an absence of in vitro expression of PPARα was observed. Docking and molecular dynamics studies revealed the plausible interaction between the synthesized compounds and PPARγ. In vivo studies established that compounds 1–4 have antihyperglycemic modes of action associated with insulin sensitization. Nitrocompound 2 was the most promising of the series, being orally active, and one of multiple modes of action could be selective PPARγ modulation due to its extra anchoring with Gln-286. In conclusion, we demonstrated that nitrocompound 2 showed strong in vitro and in vivo effects and can be considered as an experimental antidiabetic candidate.

scholarly journals Phytochemical Properties and Pharmcological Activities of Nicotiana Tabacum: A Review

2013 ◽  
Vol 1 (02) ◽  
pp. 74-82
Author(s):  
Aarti Rawat ◽  
Rakesh Roshan Mali
Keyword(s):  
Drug Discovery ◽  
Drug Design ◽  
In Silico ◽  
Traditional Approach ◽  
Discovery Process ◽  
Drug Discovery Process ◽  
Chemical Library ◽  
Modern Drug ◽  
Small Molecule Libraries ◽  
Hit Identification

Computational methods play a central role in modern drug discovery process. It includes the design and management of small molecule libraries, initial hit identification through virtual screening, optimization of the affinity as well as selectivity of hits and improving the physicochemical properties of the lead compounds. In this review article, computational drug designing approaches have been elucidated and discussed. The key considerations and guidelines for virtual chemical library design and whole drug discovery process. Traditional approach for discovery of a new drug is a costly and time consuming affair besides not being so productive. A number of potential reasons witness choosing the In-silico method of drug design to be a more wise and productive approach. There is a general perception that applied science has not kept pace with the advances of basic science. Therefore, there is a need for the use of alternative tools to get answers on efficacy and safety faster, with more certainty and at lower cost. In-silico drug design can play a significant role in all stages of drug development from the initial lead designing to final stage clinical development.

In silico designing of novel inhibitors for triple inhibition of Aldose Reductase, Aldose Reductase like protein 1, and Aldehyde Reductase

2019 ◽  
Vol 15 ◽  
Author(s):  
Arpita Devi
Keyword(s):  
Aldose Reductase ◽  
Active Site ◽  
In Silico ◽  
Genetic Factors ◽  
Dynamics Simulation ◽  
Aqueous Environment ◽  
Aldehyde Reductase ◽  
Homologous Proteins ◽  
Different Types ◽  
Orally Active

: Cancer is a well-known and well-studied disease. There are environmental as well as genetic factors that trigger cancer. All forms of cancer are associated with deregulation of genes and proteins. Aldose reductase, Aldose Reductase like protein 1 and Aldehyde Reductase are homologous proteins which are overexpressed in different types of cancer. They are NADPH-dependent oxidoreductases. The active site is conserved, thus there is very less substrate specificity among those proteins. In this study, novel molecules targeting the three proteins are designed. Molecular docking is performed to study the binding affinity of each ligand towards the targets. The six molecules studied are found to have better in silico affinity than tolrestat (known inhibitor) The designed molecules are predicted to be orally active. Finally, Molecular Dynamics Simulation shows that the protein ligand complexes are stable in aqueous environment.

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