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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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Publication Date
Mon Sep 30 2024
Journal Name
Journal Of Obstetrics, Gynecology And Cancer Research
Effect of a Nutritional Education Program on Mother Knowledge Regarding Their Children Nutritional Status
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Publication Date
Wed Jan 01 2020
Journal Name
International Journal Of Computing
Twitter Location-Based Data: Evaluating the Methods of Data Collection Provided by Twitter Api
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Twitter data analysis is an emerging field of research that utilizes data collected from Twitter to address many issues such as disaster response, sentiment analysis, and demographic studies. The success of data analysis relies on collecting accurate and representative data of the studied group or phenomena to get the best results. Various twitter analysis applications rely on collecting the locations of the users sending the tweets, but this information is not always available. There are several attempts at estimating location based aspects of a tweet. However, there is a lack of attempts on investigating the data collection methods that are focused on location. In this paper, we investigate the two methods for obtaining location-based dat

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Publication Date
Tue Jun 01 2021
Journal Name
Journal Of The College Of Languages (jcl)
The passive of verbs constructed with prepositions: Das Passiv der mit Präpositionen konstruierten Verben
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 Verbs in German and Arabic are of two types: active and passive. Passive voice  is a grammatical voice construction that is found in many languages.  Out of grammatical perspective, each main verb has a form in the active and one in the passive known as a "genus verbi" (type of verb). In passive voice, both in German and in Arabic, the focus is on the action itself or on the result of the action; often the perpetrator is not mentioned. In German, to conjugate verbs in the passive voice, you must know the forms of werden (to become). German uses werden  + the past participle and states it at the end of a sentence. In Arabic,

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Publication Date
Sun Dec 01 2019
Journal Name
Journal Of Economics And Administrative Sciences
Adopting statistical methods for controlling the quality of drinking water to achieve customer satisfaction
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The current research aims to adopt production quality decisions as the most important decisions , because they are accompanied by customer satisfaction through monitoring the quality of drinking water in iraq which reach through the pipeline network associated with water treatment projects of Tigris and Euphrates rivers. One of the indicators of quality control was the drawing of the C-chart by specifying the central line and the upper and lower limit of the control and the diagnosis of whether the production system as a whole within the scope of quality control or not and determine the strength and significance of the correlation between the quantities of water And actual needs for customers , the research has reached a number o

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Publication Date
Sun Mar 04 2012
Journal Name
Baghdad Science Journal
The use of laurylamine hydrocholoride CH3(CH2)11 NH3 –Cl for secondary oil recovery
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Laurylamine hydrochloride CH3(CH2)11 NH3 – Cl has been chosen from cationic surfactants to produce secondary oil using lab. model shown in fig. (1). The relationship between interfacial tension and (temperature, salinity and solution concentration) have been studied as shown in fig. (2, 3, 4) respectively. The optimum values of these three variables are taken (those values that give the lowest interfacial tension). Saturation, permeability and porosity are measured in the lab. The primary oil recovery was displaced by water injection until no more oil can be obtained, then laurylamine chloride is injected as a secondary oil recovery. The total oil recovery is 96.6% or 88.8% of the residual oil has been recovered by this technique as shown

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Publication Date
Wed Dec 30 2015
Journal Name
College Of Islamic Sciences
Historical inductive study on   Ground forces of the army during the first Abbasid era
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This study sought to give a general picture of the organizations and formations of the ground forces of the Abbasid army in its first era, in preparation and armament and continuous development of the mechanisms to help maintain the moral and spiritual morale in the fighting.
Therefore, the caliphs' interest in building the army, organizing it, arming it, choosing competent leaders, and providing them with various weapons in terms of production and storage, as well as taking care of fortifying the cities and gaps in determination and determination, and embarked on construction and restoration, where amazing speed and acted according to the circumstances. During the first Abbasid era, there were significant developments in the military

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Publication Date
Sat Mar 26 2016
Journal Name
Journal Of Materials Science: Materials In Electronics
Hydrothermal deposition of CdS on vertically aligned ZnO nanorods for photoelectrochemical solar cell application
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Publication Date
Wed Oct 28 2015
Journal Name
Journal Of Mathematics And System Science
Simulating Particle Swarm Optimization Algorithm to Estimate Likelihood Function of ARMA(1, 1) Model
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Publication Date
Wed Oct 25 2023
Journal Name
College Of Islamic Sciences
Provisions for a Muslim to be naturalized with the citizenship of non-Muslim countries
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Praise to Allah, Lord of the Worlds. Thank you very much. Blessed. As his face should be majestic and great. His authority, and may peace and blessings be upon our master Muhammad, a perpetual blessing until the Day of Judgment

And upon the God of purity, His righteous companions, and those who follow them in righteousness until the Day of Judgment. But after:-

Anyone who looks into the history of nations, peoples, and the conditions of human beings will see that naturalization as a person’s affiliation to a particular state is something that happened only in recent centuries. In ancient times, a person’s loyalty was to the tribe to which the person belonged, and he was integrated into it and attributed to it, and in

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Publication Date
Sun Dec 15 2019
Journal Name
Al-academy
Applications of Interior Space Design According to Shape Generation Systems: عبد الكريم علي حسين
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Treatises concerning analyzing the interior spaces multiplied and their directions varied, that some of them analyzed the interior space on the basis of the intellectual and philosophical affiliation or the historical period and others in the light of the concept and mechanisms of the shape. The researcher has not been able to find a research that dealt with analyzing the space within the systems of shape generation, thus it is possible to determine the research problem with the following question: to what extent is it possible to analyze the interior space based on systems of shape generation? As far as the importance of the research is concerned, it sheds light on five of the systems of the shape generation which are: Syntax, shape gra

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