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Synthesis, In Silico Prediction, and In Vitro Evaluation of Anti-tumor Activities of Novel 4'-Hydroxybiphenyl-4-carboxylic Acid Derivatives as EGFR Allosteric Site Inhibitors
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Introduction:

Allosteric inhibition of EGFR tyrosine kinase (TK) is currently among the most attractive approaches for designing and developing anti-cancer drugs to avoid chemoresistance exhibited by clinically approved ATP-competitive inhibitors. The current work aimed to synthesize new biphenyl-containing derivatives that were predicted to act as EGFR TK allosteric site inhibitors based on molecular docking studies.

Methods:

A new series of 4'-hydroxybiphenyl-4-carboxylic acid derivatives, including hydrazine-1-carbothioamide (S3-S6) and 1,2,4-triazole (S7-S10) derivatives, were synthesized and characterized using IR, 1HNMR, 13CNMR, and HR-mass spectroscopy.

Results:

Compound S4 had a relatively high pharmacophore-fit score, indicating that it may have biological activity similar to the EGFR allosteric inhibitor reference, and it scored a relatively low ΔG against EGFR TK allosteric site, indicating a high likelihood of drug-receptor complex formation. Compound S4 was cytotoxic to the three cancer cell lines tested, particularly HCT-116 colorectal cancer cells, with an IC50 value comparable to Erlotinib. Compound S4 induced the intrinsic apoptotic pathway in HCT-116 cells by arresting them in the G2/M phase. All of the new derivatives, including S4, met the in silico requirements for EGFR allosteric inhibitory activity.

Conclusion:

Compound S4 is a promising EGFR tyrosine kinase allosteric inhibitor that warrants further research.

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Mon Oct 01 2018
Journal Name
World Journal Ofexperimentalbiosciences
transformation of Saccharomyces cerevisiae by PET plasmid using lithium acetate
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Publication Date
Thu Oct 01 2015
Journal Name
Journal Of Engineering
Development of Spatial Data Infrastructure based on Free Data Integration
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In recent years, the performance of Spatial Data Infrastructures for governments and companies is a task that has gained ample attention. Different categories of geospatial data such as digital maps, coordinates, web maps, aerial and satellite images, etc., are required to realize the geospatial data components of Spatial Data Infrastructures. In general, there are two distinct types of geospatial data sources exist over the Internet: formal and informal data sources. Despite the growth of informal geospatial data sources, the integration between different free sources is not being achieved effectively. The adoption of this task can be considered the main advantage of this research. This article addresses the research question of ho

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Crossref
Publication Date
Thu Apr 26 2012
Journal Name
The First Scientific Conference The Collage Of Education For Pure Sciences
Solution of Third Order Ordinary BVPs Using Osculatory Interpolation Technique
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The aim of this paper is to present a method for solving third order ordinary differential equations with two point boundary condition , we propose two-point osculatory interpolation to construct polynomial solution. The original problem is concerned using two-points osculatory interpolation with the fit equal numbers of derivatives at the end points of an interval [0 , 1] . Also, many examples are presented to demonstrate the applicability, accuracy and efficiency of the method by compared with conventional method .

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Publication Date
Sun Oct 08 2023
Journal Name
European Scholar Journal
THE EFFECT OF AGILE MANUFACTURING STRATEGY ON TOTAL PRODUCTIVE MAINTENANCE
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This research aims to analyze the impact of effective manufacturing strategy on total productive maintenance. Effective manufacturing focuses on improving product quality, increasing productivity, and reducing costs, while total productive maintenance focuses on maintaining machines and equipment in good operational condition and high efficiency. The research seeks to understand how to achieve integration between these two dimensions to achieve excellent performance in manufacturing operations. The study was conducted using the General Company for Battery Manufacturing as a research community, with a sample size of 60 individuals. The research found significant results, including the fact that using an effective manufacturing strategy leads

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Publication Date
Mon Jan 01 2024
Journal Name
Communications In Computer And Information Science
Automatic Identification of Ear Patterns Based on Convolutional Neural Network
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Biometrics represent the most practical method for swiftly and reliably verifying and identifying individuals based on their unique biological traits. This study addresses the increasing demand for dependable biometric identification systems by introducing an efficient approach to automatically recognize ear patterns using Convolutional Neural Networks (CNNs). Despite the widespread adoption of facial recognition technologies, the distinct features and consistency inherent in ear patterns provide a compelling alternative for biometric applications. Employing CNNs in our research automates the identification process, enhancing accuracy and adaptability across various ear shapes and orientations. The ear, being visible and easily captured in

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Publication Date
Thu Sep 30 2021
Journal Name
International Journal Of Research In Social Sciences And Humanities
The Anonymous Identity of Forced Migrants: A Post-Colonial Study
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Colonialism invades the Third World countries, physically and psychologically. This article exposes but sample of the physical and psychological consequences of colonialism. The Beekeeper of Aleppo (2019) by the British novelist, Christy Lefteri is a typical novel to diagnose the harsh circumstances of individuals within and after the disaster. Since it depicts characters from Asian countries, it would be a best representative for all Asian people who suffer colonialism. Migration toward anonymity is the mere option for the colonized people. Aftermath, they experience displacement, trauma, and the loss of identity.

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Crossref
Publication Date
Mon Mar 08 2021
Journal Name
Baghdad Science Journal
Improving Applied properties of poly unsaturated ester Bozafah monomers Vanalah
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Suggested in this study the introduction of monomers have the ability to interact with polyester Rzn way confused or Alchapak Vodev polycarbonate first Almiaal acrylate ????? grains and offered models for high temperature and for a period of time of 40 days and absorbance and penetration and after color changes resulting from the storage heat higher using shades where models were extractedthermal storage and take measurements and then returned periodically results were consistent with theoretical expectations and mixing

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Publication Date
Sun Jul 01 2018
Journal Name
Journal Of Aerosol Science
On the design of miniature parallel-plate differential mobility classifiers
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Publication Date
Thu Feb 01 2018
Journal Name
Journal Of Computational And Theoretical Nanoscience
Controlling of Robot Hand by Using Microcontroller with Visual Basic
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The robot arm is the most popular robotic form used in industry. Thus, it is crucial to make a system programming which could controlled the movement of each part in the industrial robot to make it works properly. One of the simplest models of the robot arm is EDARM ED-7100 which has a controller to control the movement of the robot arm manually. In this study, the robot controller has been redesigned in order to improve this robot's function. The new controller system used AT89S52 microcontroller which has wire connected to the robot hand. A function has been added with this controller to improve the system of controlling and becomes better than the previous system (only manually). The functions of the new system include three mo

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Scopus Crossref
Publication Date
Sat Jun 30 2012
Journal Name
Al-kindy College Medical Journal
Treatment of Nasopharyngeal Carcinoma by Using Deep X-Ray Therapy
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Background: Nasopharyngeal carcinoma (NPC) is one of the most challenging tumors because of their relative inaccessibility and that their spread can occur without significant symptoms with few signs, but Radiotherapy (RT) has a role in treatment of it.
Objectives: To show that RT is still the modality of choice in the treatment of NPC, to study modes of presentations, commonest histopathological types and their percentages, to show differences in the sensitivities of these types to RT and to find out a 5 year survival rate(5YSR) and its relation with lymph node involvement.
Methods: This is a retrospective study of 44 patients with NPC who were treated with routine RT from 1988-2007 at the institute of radiology and nuclear medicin

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