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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
Tue Mar 30 2021
Journal Name
Journal Of Economics And Administrative Sciences
The Bayesian Estimation for The Shape Parameter of The Power Function Distribution (PFD-I) to Use Hyper Prior Functions
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The objective of this study is to examine the properties of Bayes estimators of the shape parameter of the Power Function Distribution (PFD-I), by using two different prior distributions for the parameter θ and different loss functions that were compared with the maximum likelihood estimators. In many practical applications, we may have two different prior information about the prior distribution for the shape parameter of the Power Function Distribution, which influences the parameter estimation. So, we used two different kinds of conjugate priors of shape parameter θ of the <

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Publication Date
Sun Jun 30 2024
Journal Name
International Journal Of Intelligent Engineering And Systems
Development of Intelligent Control Strategy for an Anesthesia System Based on Radial Basis Function Neural Network Like PID Controller
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Publication Date
Wed May 03 2017
Journal Name
Arab Conferences Network / American Research Foundation
Understanding the nature of science among chemistry teachers according to the AAAS document for the Educational Reform Project 2061
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Publication Date
Thu Jun 01 2017
Journal Name
Journal Of Economics And Administrative Sciences
Compared of estimating two methods for nonparametric function to cluster data for the white blood cells to leukemia patients
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Abstract:                                        

   We can notice cluster data in social, health and behavioral sciences, so this type of data have a link between its observations and we can express these clusters through the relationship between measurements on units within the same group.

    In this research, I estimate the reliability function of cluster function by using the seemingly unrelate

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Publication Date
Wed Oct 31 2018
Journal Name
International Journal Of Research In Pharmaceutical Sciences
The impact of systemic hypertension-related heart remodeling on right ventricle mechanics: A two-dimensional echocardiographic speckle tracking study
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Publication Date
Wed Dec 12 2018
Journal Name
Iop Conference Series: Materials Science And Engineering
The performance of MnO<sub>2</sub>/graphite electrode for TOC removal from wastewater by indirect electrochemical oxidation process
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Electrochemical oxidation in the presence of sodium chloride used for removal of phenol and any other organic by products formed during the electrolysis by using MnO2/graphite electrode. The performance of the electrode was evaluated in terms fraction of phenol and the formed organic by products removed during the electrolysis process. The results showed that the electrochemical oxidation process was very effective in the removal of phenol and the other organics, where the removal percentage of phenol was 97.33%, and the final value of TOC was 6.985 ppm after 4 hours and by using a speed of rotation of the MnO2 electrode equal to 200 rpm.

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Publication Date
Tue Mar 08 2022
Journal Name
Multimedia Tools And Applications
Comparison study on the performance of the multi classifiers with hybrid optimal features selection method for medical data diagnosis
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Publication Date
Tue Mar 21 2023
Journal Name
International Journal Of Interactive Mobile Technologies (ijim)
Study the Effect of Using Google Classroom on the Academic Performance Under the Covid19 Pandemic Using Data Mining Technique
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— In light of the pandemic that has swept the world, the use of e-learning in educational institutions has become an urgent necessity for continued knowledge communication with students. Educational institutions can benefit from the free tools that Google provide and from these applications, Google classroom which is characterized by ease of use, but the efficiency of using Google classroom is affected by several variables not studied in previous studies Clearly, this study aimed to identify the use of Google classroom as a system for managing e-learning and the factors affecting the performance of students and lecturer. The data of this study were collected from 219 members of the faculty and students at the College of Administra

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Publication Date
Fri Dec 01 2023
Journal Name
Al-khwarizmi Engineering Journal
The Remediation of Congo Red-Contaminated Groundwater by using a Permeable Reactive Barrier Through Modified Waterworks Sludge MgAl-LDH
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This investigation aims to explore the potential of waterworks sludge (WS), low-cost byproduct of water treatment processes, as a sorbent for removing Congo Red (CR) dyes. This will be achieved by precipitating nano-sized (MgAl-LDH)-layered double hydroxide onto the surface of the sludge. The efficiency of utilizing MgAl-LDH to modify waterworks sludge (MWS) for use in permeable reactive barrier technology was confirmed through analysis with Fourier transform infrared and X-ray diffraction. The isotherm model was employed to elucidate the adsorption mechanisms involved in the process. Furthermore, the COMSOL model was utilized to establish a continuous testing model for the analysis of contaminant transport under diverse conditions. A st

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Publication Date
Sun Mar 07 2010
Journal Name
Baghdad Science Journal
Improvement the bearing capacity of the soil which is supporting the shallow foundation by using bored short micro-piles
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In this paper , concrete micro-piles were used to improve the bearing capacity of the soil which is supporting the shallow foundation by using groups of (4; 6 and 9)bored short micro-piles which have, (D=0.125m and D=0.1m), and length to diameter ratio (L/D) equal to (6; 10 and 12) respectively. To calculate the bearing capacity of the micro-piles,(Tomlinson) and (Lamda) methods were used; also the soil properties were taken from Al-Muthana airport,(Al-Qyssi,2001) [1]. The results show that; increasing the number of piles and/ or the diameters and lengths; and the interaction between the bearing capacity of the shallow foundation with the bearing capacity of the pile group which leads to increasing the strength against the external loads

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