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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
Fri Jun 01 2018
Journal Name
Journal Of Accounting And Financial Studies ( Jafs )
Impact of the Lean Thinking on the Rationalization Costs & Achieving Customer Satisfaction: An applied Research at Ur State company Electrical Cables industries
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The research explored the impact of applying lean thinking With all that carries this term of goals, trends, principles, foundations and concepts, The possibility of applying it in institutions, including Ur public company, an industrial company, And the only one in Iraq specialized in the manufacture of cables, Electrical Wires and the aluminum industry ,Which has been applied to the curriculum of lean thinking , The problem of research is that the institutions, including the company (research sample), adopt and practice traditional administrative, financial and technical methods without relying on modern curricula and ideas, including the subject of our research, In order to achieve the research objectives, the research was divided int

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Publication Date
Mon May 01 2023
Journal Name
Human Gene
The G allele of the ADAM33 T1 polymorphism (rs2280091) is a risk factor associated with asthma severity among the Iraqi Arab population
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Background: The gene encoding a disintegrin and metalloproteinase domain 33 (ADAM33) is known to be associated with asthma in different ethnic groups. In Iraq, among the Arab ethnic background, this association has not yet been highlighted. Methods: One hundred and ninety-two asthmatics were examined; 118 males and 74 females (mean age 38.23 ± 9.13 years). The control group was 183; 110 males and the rest were females. The SNP of rs2280091 A/G (T1) was studied here to determine adam33 genotyping status using polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP). The level of total IgE was measured using enzyme-linked immunosorbent assay (ELISA). Results: Significant differences (p = 0.004) in the frequencies of

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Publication Date
Sun May 25 2025
Journal Name
Al–bahith Al–a'alami
Tweets of Iraqi Political Leaders Regarding The Movement to Form The Governmet Through Twitter (From 3rd Septemper 2018 To 3rd Septemper 2019)
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This research analyses the tweets of Iraqi politicians (leaders) that took place simultaneously with the formation of the Iraqi government after the elections in 2018. The formation of the Iraqi government was considered one of the most critical issues that emerged in the political process to which the Iraqi media as well as social networking sites paid considerable attention. In this regard, Iraqi political leaders have published many tweets concerning the formation of the government, some of them have caused great controversy in the political climate. As Twitter is one of the most digital platforms that have been widely used on the global scale in recent years, politicians have employed it to publish their opinions, ideas, and to excha

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Publication Date
Thu Aug 01 2019
Journal Name
International Journal Of Research - Granthaalayah
MULTIPLE MIXING RATIOS OF GAMMA RAY TRANSITIONS FROM 𝟔𝟎𝐍𝐝 𝟏𝟒𝟐− 𝟏𝟓𝟎 (𝐧, 𝐧 ˊ𝛄) 𝟔𝟎𝐍𝐝 𝟏𝟒𝟐− 𝟏𝟓𝟎 REACTION USING 𝒂𝟐- RATIO METHOD
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In the current work, the mixing ratios ( 𝛿 ) of gamma transitions were calculated from energy levels in the isotopes neodymium 60𝑁𝑎 142−150 populated in the 60Nd 142− 150 (n, n ˊγ) 60Nd 142− 150 using the 𝑎2 ratio method. We used the experimental coefficient (𝑎2 ) for two γ-transitions from the initial state itself, the statistical tensor 𝜌2(𝐽𝑖), associated with factor 𝑎2 , would be the same for the two transitions. The results obtained are in good agreement or within the experimental error with -those previously published. And existing contradictions resulting from inaccuracies in the empirical results of previous work. The current results confirm that the , 𝑎2 − method is used to calculate th

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Publication Date
Fri Jun 28 2019
Journal Name
Journal Of The College Of Education For Women
The Effectiveness of an Educational Program For Early Intervention depending on Illustrative Pictures to Acquire some concepts For Children with Hearing impairment
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“Child of today is a man of the future" this slogan is one of the most popular logos of international organizations and institutions that dealing with human beings needs in general and children needs in particular, whether these needs are educational, health, social, or economic. Children require special care and extra legal protection, since the child-raising is not the Child’s own issue, but it's the issue of the society in which he/she would integrate.

As the education and language skillsacquisition primarily associated with hearing, because human being receives most of the skills and knowledge through the hearing; that imitate sounds and learn how to speak isacquired only by hearing, so therefore the hearing - impairedchi

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Publication Date
Mon Dec 20 2021
Journal Name
Bulletin Of The Iraq Natural History Museum (p-issn: 1017-8678 , E-issn: 2311-9799)
MOLECULAR CHARACTERIZATION OF ANISAKID NEMATODES HYSTEROTHYLACIUM SPECIES FROM JAPANESE THREADFIN BREAM NEMIPTERUS JAPONICUS (BLOCH, 1791) (PERCIFORMES, NEMIPERIDAE) FROM IRAQI MARINE WATER FISH
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The present study provides a new insight into valuable information on the diverse structure of the Anisakid population and discusses the limited species richness in the Nemipterus japonicus (Bloch,1791) (Perciformes, Nemiperidae). The fishing area consists of various locations in the Arabian Gulf (29°58 0 33 00 N48°28 0 20 E). A total of 315 marine fish were examined, (n=287) were infected. Larval stages (n= 763) encysted within the mesenteries peritoneum and viscera of fish organs were isolated, with a prevalence of 91.11% of infection and, the intensity was 2.65. Molecular analysis was carried out on thirty individuals who have examined the morphology and showed some appearance differences, by amplifying internal transcribed spacers

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Publication Date
Sat Jan 01 2022
Journal Name
Optik
Plasma parameters of Au nano-particles ablated on porous silicon produced via Nd-YAG laser at 355 nm for sensing NH3 gas
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a laser ablation Q-switched Nd: YAG laser with a wave-length of 355 nm at a variety of laser pulse energies (E) and deposited on porous silicon (PS). Optical emission spectrometer was used to diagnosed medium air to study gold plasma characteristics and prepared Au nanoparticles. The laser pulse energy influence has been studied on the plasma characteristics in air. The data showed the emergence of the ionic (Au II) spectral emission lines in the gold plasma emission spectrum. XRD has been utilized to examine structural characteristics. Moreover, AFM results 37.2 nm as the mean value of the diameter that is coordinated in a shape similar to the rod that appears for Au NPs, in addition to that, TEM has been an indication of the fact that syn

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Publication Date
Fri Jan 01 2021
Journal Name
Indonesian Journal Of Electrical Engineering And Computer Science
BotDetectorFW: an optimized botnet detection framework based on five features-distance measures supported by comparisons of four machine learning classifiers using CICIDS2017 dataset
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<p><span>A Botnet is one of many attacks that can execute malicious tasks and develop continuously. Therefore, current research introduces a comparison framework, called BotDetectorFW, with classification and complexity improvements for the detection of Botnet attack using CICIDS2017 dataset. It is a free online dataset consist of several attacks with high-dimensions features. The process of feature selection is a significant step to obtain the least features by eliminating irrelated features and consequently reduces the detection time. This process implemented inside BotDetectorFW using two steps; data clustering and five distance measure formulas (cosine, dice, driver &amp; kroeber, overlap, and pearson correlation

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Publication Date
Sat May 01 2021
Journal Name
Journal Of Physics: Conference Series
Violet Laser Irradiation Effect on The Optical Properties of Cobalt oxide (CoO<sub>2</sub>) Thin Films deposited via Semi-Computerized Spraying System
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Abstract<p>The existing investigation explains the consequence of irradiation of violet laser on the optic properties of (CoO<sub>2</sub>) films. The film was equipped by the utilization of semi-computerized spray pyrolysis technique (SCSPT), it is the first time that this technique is used in the preparation and irradiation using a laser in this technique. From the XRD analysis, the crystalline existence with trigonal crystal system was when the received films were processed by continuous violet laser (405 nm) with power (1W) for different laser irradiation time using different number of times a laser scan (0, 6, 9, 12, 15 and 18 times) with total irradiation time(0,30,45,60,75,90 min</p> ... Show More
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Publication Date
Fri Jan 01 2016
Journal Name
Journal Of Engineering
A Mathematical Model of a Thermally Activated Roof (TAR) Cooling System Using a Simplified RC-Thermal Model with Time Dependent Supply Water Temperature
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This paper presents a computer simulation model of a thermally activated roof (TAR) to cool a room using cool water from a wet cooling tower. Modeling was achieved using a simplified 1-D resistance-capacitance thermal network (RC model) for an infinite slab. Heat transfer from the cooling pipe network was treated as 2-D heat flow. Only a limited number of nodes were required to obtain reliable results. The use of 6th order RC-thermal model produced a set of ordinary differential equations that were solved using MATLAB - R2012a. The computer program was written to cover all possible initial conditions, material properties, TAR system geometry and hourly solar radiation. The cool water supply was considered time

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