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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
Thu Mar 01 2018
Journal Name
International Journal Of Mechanical Engineering And Technology (ijmet)
Information model of plastic products formation process duration by injection molding method
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Scopus (5)
Scopus
Publication Date
Tue Sep 11 2018
Journal Name
Iraqi Journal Of Physics
Manufacturing of porous refractories from Iraqi Kaolin by adding expanded polystyrene waste
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Fabrication of porous clay refractory insulating specimens from Iraqi kaolin with different percentage of Expanded Polystyrene (EPS) waste crumbs additions were investigated. After mixing and forming by hand molding, the specimens was dried and fired at 1300 oC. The structural, physical, mechanical and thermal properties of the refractory insulating products were measured. Maximum addition of EPS (1.25 wt%) lead to reduce the linear shrinkage to less than 1.7% and increased apparent porosity up to 50 %. As well as, the density, Modulus of rupture and thermal conductivity were reduced to 1.39 g/cm3, 4.1 MPa and 0.21 W/m.K, respectively. The final outcome, addition of EPS showed good results in the formation of pores without distorting the

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Publication Date
Tue Aug 15 2023
Journal Name
Al-academy
The shapes of adjacent structures for informing the stage show for children
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This research talked about the importance of adjacent structures for informing the stage show for children. The researcher began from the importance of adjacent structures for informing the show to introduce the various and different proofs, on the level of creativity and artistic shape of the accomplishment over it’s shifts that contribute to formation the show and it's intellectual, artistic, technical and cognitive Marks that contribute in dynamism the interactive show and contact the idea that connect with the design and directional vision for the beauty and cognitive. Lead to the eager operation in attention, sensitive and attractive the child. The research consist of four chapters: The first chapter include methodological framewo

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Publication Date
Mon Jun 19 2023
Journal Name
Journal Of Engineering
Structural Behavior of Reinforced Concrete Hollow Beams under Partial Uniformly Distributed Load
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A Longitudinal opening is used to construct hollow core beam is a cast in site or precast or pre stressed concrete member with continuous voids provided to reduce weight, cost and, as a side benefit, to use for concealed electrical or mechanical runs. Primarily is used as floor beams or roof deck systems. This study investigate the behavior of six beams (solid or with opening) of dimension (length 1000 x height 180 x width120mm) simply support under partial uniformly distributed load, four of these beam contain long opening of varied section (40x40mm) or (80x40mm). The effect of vertical steel reinforcing, opening size and orientations are investigated to evaluate the response of beams. The experimental behavior based on load-deflection

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Publication Date
Wed Nov 01 2023
Journal Name
Solar Energy
Optimizing performance of water-cooled photovoltaic-thermal modules: A 3D numerical approach
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To evaluate and improve the efficiency of photovoltaic solar modules connected with linear pipes for water supply, a three-dimensional numerical simulation is created and simulated via commercial software (Ansys-Fluent). The optimization utilizes the principles of the 1st and 2nd laws of thermodynamics by employing the Response Surface Method (RSM). Various design parameters, including the coolant inlet velocity, tube diameter, panel dimensions, and solar radiation intensity, are systematically varied to investigate their impacts on energetic and exergitic efficiencies and destroyed exergy. The relationship between the design parameters and the system responses is validated through the development of a predictive model. Both single and mult

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Publication Date
Wed Jan 01 2020
Journal Name
Fme Transactions
Development of automated liquid filling system based on the interactive design approach
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The automatic liquid filling system is used in different applications such as production of detergents, liquid soaps, fruit juices, milk products, bottled water, etc. The automatic bottle filling system is highly expensive. Where, the common filling systems required to complex changes in hardware and software in order to modify volume of liquid. There are many important variables in the filling process such as volume of liquid, the filling time, etc. This paper presents a new approach to develop an automatic liquid filling system. The new proposed system consists of a conveyor subsystem, filling stations, and camera to detect the level of the liquid at any instant during the filling process. The camera can detect accurately the leve

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Publication Date
Mon Jan 28 2019
Journal Name
Journal Of The College Of Education For Women
The Social Motive Behind the Inclusion of Moses Story Within Andalusi Poetry
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The significance of the social motivation lies in showing the great and important role of the story of the prophet of ( Moser ( Peace upon him) in Quran , especially , it is considered the greatest one in Quran , as that confirmed by the poets of Andalusera ,as it includes aspects similar to that prevailing over in their environments and their social life via the social motivation. Moreover , the relation's poets with the Andalus society where suitability prevailing over consistent with the events of the story; bedsides, artistic expression about the society for being considered as a trust mirror reflect real facts surrounded by the Andalussociety with all its sides and aspects . Thus , the poet takes Quran , especially the story of Mose

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Publication Date
Thu May 05 2016
Journal Name
Global Journal Of Engineering Science And Researches
EVALUATE THE RATE OF CONTAMINATION SOILS BY COPPER USING NEURAL NETWORK TECHNIQUE
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The aim of this paper is to design suitable neural network (ANN) as an alternative accurate tool to evaluate concentration of Copper in contaminated soils. First, sixteen (4x4) soil samples were harvested from a phytoremediated contaminated site located in Baghdad city in Iraq. Second, a series of measurements were performed on the soil samples. Third, design an ANN and its performance was evaluated using a test data set and then applied to estimate the concentration of Copper. The performance of the ANN technique was compared with the traditional laboratory inspecting using the training and test data sets. The results of this study show that the ANN technique trained on experimental measurements can be successfully applied to the rapid est

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Publication Date
Thu Mar 30 2023
Journal Name
Journal Of Economics And Administrative Sciences
An Artificial Intelligence Algorithm to Optimize the Classification of the Hepatitis Type
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Hepatitis is one of the diseases that has become more developed in recent years in terms of the high number of infections. Hepatitis causes inflammation that destroys liver cells, and it occurs as a result of viruses, bacteria, blood transfusions, and others. There are five types of hepatitis viruses, which are (A, B, C, D, E) according to their severity. The disease varies by type. Accurate and early diagnosis is the best way to prevent disease, as it allows infected people to take preventive steps so that they do not transmit the difference to other people, and diagnosis using artificial intelligence gives an accurate and rapid diagnostic result. Where the analytical method of the data relied on the radial basis network to diagnose the

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Publication Date
Sun Jun 07 2026
Journal Name
Journal Of Engineering
Technological Analysis of Flat Surface Conditions by Magnetic Abrasive Finishing Method (MAF)
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This study introduced the effect of using magnetic abrasive finishing method (MAF) for finishing flat surfaces. The results of experiment allow considering the MAF method as a perspective for finishing flat surfaces, forming optimum physical mechanical properties of surfaces layer, removing the defective layers and decreasing the height of micro irregularities. Study the characteristics which permit judgment parameters of surface quality after MAF method then comparative with grinding

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