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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
Sat Aug 27 2022
Journal Name
Revista Electronica De Veterinaria
Hepatoprotective Activity of Plantago Lanceolata Aqueous Extract on Albino Female Mice
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This study gives an overview of the widely distributed herb plantain Plantago lanceolata and aqueous extraction of the plant, by study the effect of Plantago lanceolata aqueous extract on the hepatoprotective activity in albino female mice through measuring the three main liver enzymes aspartate transaminase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP) with the histological effect of extract on liver. Mice were separated into eight groups treated intraperitonially for seven days: (1) control, (2) CCl4 (0.02%), (3) aqueous extract (250 mg/kg), (4) aqueous extract (500 mg/kg), (5) CCl4 (0.02%) plus aqueous extract (250 mg/kg), (6) CCl4 (0.02%) plus aqueous extract (500 mg/kg),(7) aqueous extract (250 mg/kg) plus CCl4 (0.02

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Publication Date
Thu Aug 01 2024
Journal Name
Iop Conference Series: Earth And Environmental Science
Evaluating the Structural Integrity of Cellular Steel Beams with Web Enhancements
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Abstract<p>This study investigates the analytical approach of web reinforcement techniques, including high-strength concrete and laced reinforcement, to enrich improvement for the structural behavior of these beams. The analysis compares an unmodified cellular beam (LB1) with a web-reinforced beam (LB2), including the improvements in load-carrying capacity. The study considers the effects of reinforcement on critical design limit states, such as flexural strength, Vierendeel bending, web post-buckling, and shear resistance. The outcomes reveal significant enhancements in LB2’s structural behavior, with over a 100% increase in flexural strength and local axial force capacity and a 165% increase</p> ... Show More
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Publication Date
Wed Jul 01 2026
Journal Name
Nature Communications
Structural basis for independent pore function of Vpb4 from Bacillus thuringiensis
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Abstract<p> The Bacterial_Exotoxin_B family constitutes translocating pore-forming proteins that function as the binding (B) component in the binary AB Toxin mechanism. While the two-component system of the family is consistent among well-characterised members, the single-component Vpb4 subclass from entomopathogenic <italic>Bacillus thuringiensis</italic> challenges this dogma. Here, through single-particle cryo-electron microscopy, we elucidate the inserted pore structure of a Vpb4 member, Vpb4Aa2, at 2.2 Å resolution. The structure reveals distinguishing features from other family members: missing molecular bottleneck</p> ... Show More
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Publication Date
Thu Mar 21 2024
Journal Name
Egyptian Journal Of Medical Human Genetics
Low heterozygosity for rs3811050, a 5 prime untranslated region variant of the gene encoding interleukin-38 (IL1F10), is associated with a reduced risk of systemic lupus erythematosus
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Abstract<sec> <title>Background

Interleukin-38 (IL-38), an inflammatory cytokine discovered in recent years, has been implicated in the pathogenesis of systemic lupus erythematosus (SLE). IL-38 is encoded by the IL1F10 (interleukin 1 family member 10) gene. Genetic variants of this gene have been associated with susceptibility to a number of autoimmune and inflammatory diseases, while their association with SLE risk has not been explored. In this case–control study, two novel variants of the 5 prime untranslated region (5′UTR) of the IL1F10 gene, rs3811050 C/T and rs3811051 T/G, were investigated

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Publication Date
Sun Aug 30 2020
Journal Name
Journal Of Economics And Administrative Sciences
Proposing Robust IRWs Technique to Estimate Segmented Regression Model for the Bed load Transport of Tigris River with Change Point of Water Discharge Amount at Baghdad City
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Segmented regression consists of several sections separated by different points of membership, showing the heterogeneity arising from the process of separating the segments within the research sample. This research is concerned with estimating the location of the change point between segments and estimating model parameters, and proposing a robust estimation method and compare it with some other methods that used in the segmented regression. One of the traditional methods (Muggeo method) has been used to find the maximum likelihood estimator in an iterative approach for the model and the change point as well. Moreover, a robust estimation method (IRW method) has used which depends on the use of the robust M-estimator technique in

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Publication Date
Sat Aug 29 2026
Journal Name
Journal Of Physical Education
The Effect of Exercises Using Maximum Strength Assisting Training Apparatus On Some Working Muscles&#39; Electric Activity During Bench Press For Physical Strength Athletes Of Baghdad Clubs
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Publication Date
Fri Nov 01 2024
Journal Name
مجلة بحوث الشرق الأوسط
أثر أنموذج وودز في تحصيل مادة البلاغة عند طالبات المرحلة الاعدادية The effect of the Woods model on the achievement of rhetoric among female middle school students
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Publication Date
Mon Nov 15 2021
Journal Name
Aip Conference Proceedings
Oil skimming followed by coagulation/flocculation processes for oilfield produced water treatment and zero liquid discharge system application
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The study focused on the treatment of real oilfield produced water from the East Baghdad field affiliated to the Midland Oil Company (Iraq) using an oil skimming process followed by a coagulation/flocculation process for zero liquid discharge system applications. Belt type oil skimmer was utilized for evaluating the process efficiency with various operating conditions such as temperature (17-40 °C) and time (0.5-2.5 hr.). Polyaluminum chloride (PAC) coagulant and polyacrylamide (PAM) flocculant was used to investigate the performance of the coagulation/flocculation process with PAC dosage (5-90 ppm) and pH (5-10) as operating conditions. In the skimming process, the oil content, COD, turbidity, and TSS decreased with an increase in tempera

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Publication Date
Tue Jan 29 2019
Journal Name
Journal Of The College Of Education For Women
Thinking skills and its Relationship to Some Variables to Four Grade Primary School Pupils with Slow Learning Abilities
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The problem of slow learning in primary schools’ pupils is not a local or private one. It is also not related to a certain society other than others or has any relation to a particular culture, it is rather an international problem of global nature. It is one of the well-recognized issues in education field. Additionally, it is regarded as one of the old difficulties to which ancient people gave attention. It is discovered through the process of observing human behaviour and attempting to explain and predict it.
Through the work of the two researchers via frequent visits to primary schools that include special classes for slow learning pupils, in addition to the fact that one of the researcher has a child with slow learning issue, t

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Publication Date
Mon Oct 01 2018
Journal Name
Journal Of Economics And Administrative Sciences
The Causal Relationship between Stock Market Indices Volatility and Oil Prices Volatility: Empirical Evidence from Iraqi Stock Exchange
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The study investigates the relationship between the volatility of the Iraqi Stock Exchange Index (ISX), and the volatility of global oil prices benchmarks, Brent and West Intermediate Texas (WTI), in additional to the Iraqi Oil, Basra Crude Light (BSL) which represents the most exported Iraqi oil and the major influential factor on the Iraqi governmental revenues. Using monthly data covering the period: 1/2005-12/1205, econometrical and technical tools represented by Co-incretion, Vector Error Correction Model – VECM, Granger Causality, and Bollinger band were employed in order to explore the relationship between the variables.

The econometric analysis revealed the impact of the oil prices volatility on

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