In Silico and In Cell Hybrid Selection of Nonrapalog Ligands to Allosterically Inhibit the Kinase Activity of mTORC1

Author(s):  
Raef Shams ◽  
Akihiro Matsukawa ◽  
Yukari Ochi ◽  
Yoshihiro Ito ◽  
Hideyuki Miyatake
Author(s):  
Yorick Bernardus Cornelis van de Grift ◽  
Nika Heijmans ◽  
Renée van Amerongen

AbstractAn increasing number of ‘-omics’ datasets, generated by labs all across the world, are becoming available. They contain a wealth of data that are largely unexplored. Not every scientist, however, will have access to the required resources and expertise to analyze such data from scratch. Fortunately, a growing number of investigators is dedicating their time and effort to the development of user friendly, online applications that allow researchers to use and investigate these datasets. Here, we will illustrate the usefulness of such an approach. Using regulation of Wnt7b expression as an example, we will highlight a selection of accessible tools and resources that are available to researchers in the area of mammary gland biology. We show how they can be used for in silico analyses of gene regulatory mechanisms, resulting in new hypotheses and providing leads for experimental follow up. We also call out to the mammary gland community to join forces in a coordinated effort to generate and share additional tissue-specific ‘-omics’ datasets and thereby expand the in silico toolbox.


1990 ◽  
Vol 7 (4) ◽  
pp. 80-86
Author(s):  
Jaemog Soh ◽  
Sidney Pestka

Author(s):  
Vinod Kumar Gurjar

Abstract: The extremely drug resistant may be a worldwide public ill health in recent years. Molecules with newer targets and an alternate mechanism of action is an urgent requirement of improvement of latest drugs. The utilization of heterocyclic compounds has been increased dramatically over the last 70 years due to their wide selection of technical applications and their favorable environmental and toxicological properties The 1,8-naphthyridine and quinoline 3-carboxylic acid derivatives that we'll manufacture during this method will change the potency and specificity of fluoroquinolones. Taking under consideration the findings, the goal is to style and manufacture 1, 8-naphthyridine and quinoline 3-carboxylic acid derivatives. The synthesized compounds are going to be characterized using multiple analytical techniques, virtual screening, and in-silico ADME/T prediction. Keywords: 1, 8-Naphthyridine, Quinoline, ADMET, Heterocyclic Compound


2007 ◽  
Vol 21 (4) ◽  
pp. 167-188 ◽  
Author(s):  
Yovani Marrero-Ponce ◽  
Mahmud Tareq Hassan Khan ◽  
Gerardo M. Casañola-Martín ◽  
Arjumand Ather ◽  
Mukhlis N. Sultankhodzhaev ◽  
...  

Author(s):  
Sailu Sarvagalla ◽  
Mohane Selvaraj Coumar

Most of the developed kinase inhibitor drugs are ATP competitive and suffer from drawbacks such as off-target kinase activity, development of resistance due to mutation in the ATP binding pocket and unfavorable intellectual property situations. Besides the ATP binding pocket, protein kinases have binding sites that are involved in Protein-Protein Interactions (PPIs); these PPIs directly or indirectly regulate the protein kinase activity. Of recent, small molecule inhibitors of PPIs are emerging as an alternative to ATP competitive agents. Rational design of inhibitors for kinase PPIs could be carried out using molecular modeling techniques. In silico tools available for the prediction of hot spot residues and cavities at the PPI sites and the means to utilize this information for the identification of inhibitors are discussed. Moreover, in silico studies to target the Aurora B-INCENP PPI sites are discussed in context. Overall, this chapter provides detailed in silico strategies that are available to the researchers for carrying out structure-based drug design of PPI inhibitors.


LWT ◽  
2020 ◽  
Vol 130 ◽  
pp. 109617
Author(s):  
Selvakumar Vijayalakshmi ◽  
Damilare Emmanuel Adeyemi ◽  
In Young Choi ◽  
Ghazala Sultan ◽  
Inamul Hasan Madar ◽  
...  

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