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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 Nov 21 2025
Journal Name
Journal Of Baghdad College Of Dentistry
The effect of curvature angle and rotational speed on the cyclic fatigue of three types of rotary instrument (In vitro): comparative study
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Background: The fracture of instruments within root canal during endodontic treatment is a common incidence, fracture because of fatigue through flexure occurs due to metal fatigue, this study aimed to assess the effect of curvature angle and rotational speed on the cyclic fatigue of different type of Endodontic NiTi Rotary Instruments and compare among them. Materials and method: Three types of rotary instruments with tip size 0.25: ProTaPer F2 (Densply, Malifier) Revo-S SU( 0.06 taper, MicroMega) and RaCe system (0.06 taper, FKG, Dentaire), Forty file of each instrument were used within two canals with angle of curvature (40 &60 )at two speed (250&400)RPM, twelve group were formed for all instruments(total number=120),ten file fo

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Publication Date
Tue Jun 01 2021
Journal Name
Journal Of Engineering
Evaluation of Using Magnetized Water in Leaching Salts in Sandy Loam Soil
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Many studies and researchers have reported significant evidence that some physical properties of water can be changed as it passes through a magnetic field that can improve water use.  This can have a promising potential for applications, especially in the fields of irrigation and drainage. In this research, magnetized water was used to leach salt-affected sandy loam soil. A test rig was designed and constructed to investigate the effects of magnetized water on leaching soil. The rig consists of a magnetization device that can provide variable intensity. Water was supplied from a constant head reservoir to the magnetization device then to the soils that were placed in plastic columns. Five different magnetic intensi

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Publication Date
Wed Oct 17 2018
Journal Name
Journal Of Economics And Administrative Sciences
Impact of evaluation of investment projects in achieving competitive strategy
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The aim of the research is to determine the impact of evaluation of investment projects after the preparation of investment budgets taking into consideration within the investment budgets the concept of competitive strategy, as the harmony between the preparation of investment budgets and competitive strategy will contribute to the success of economic unity and achieve profits well and achieve a competitive advantage. Strategies for economic units because the most important factor to them is the costs produced and the progress of the research problem is focused on "Is it possible to include a strategy of competition, especially within the investment budget when prepared The study concluded that the investment plan prepared by the

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Publication Date
Fri Nov 21 2025
Journal Name
Journal Of Babylon Center For Humanities Studies
Reflection of Zionism in the literature of the Jews of Iraq ... Read in the novel "The Dove Flyer" by Elie Amir
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The upbringing of Yehuda Amichai and the conditions he lived in had a great influence on his deep sense of pain, which made him think of death and suicide. Especially after the Nazis came to power in Germany, and his emigration with his family. Amichai searched for love throughout his life, and his failure was one of the most important factors affecting his psyche, which is A deep influence that made him live in harsh and painful pains that broke him, and prevented her from achieving his ambitions in life.Dramatic texts are characterized by repetition in writing and presentation. It is a textual discourse that has two advantages, first, that it can be read as a literary text like all other literary texts, and second, that it can be consider

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Publication Date
Thu Mar 01 2012
Journal Name
Journal Of Economics And Administrative Sciences
The Role Of Information Technology In Enhancing Performance Evaluation And Responsibility Accounting (Empirical Study In Jordan Hotels )
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   This paper suggesting a new modern method to evaluate the performance of hotel industry at Jordan instead of the classical method used by the industry and that is Bench Marking , this method can be done by comparing the performance of hotel industry at two serial years which helps in calculating a standard performance .

  The industry can use this standard to identify the variance, which make the evaluation of performance easier and support the efforts to develop the hotel industry at all levels and enable to give high quality services to customers.

    The study believed that this situation would not be achieved unless the hotel industry will app

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Publication Date
Wed Feb 01 2023
Journal Name
Baghdad Science Journal
Evaluation of Beta-2 Integrin and Platelets Roles in Sickle Cell Disease Pathogenicity in Basrah Governorate Patients
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Sickle cell disease (SCD) comprises an inherited blood disorder that is life long and affects many people globally. In spite of the development in treatment, SCA is a considerable cause of mortality and morbidity. The present study tries to assess the role of leukocytes represented by β integrin(CD18) and platelets and their productivity in the pathogenicity of disease during  the steady state and crisis in comparison with the healthy as-control group, SCD patients (15) enrolled during crisis and steady state (follow up) showed a significant increase in leukocytes and platelets cells productivity during crisis when compared to the steady state and in the steady state when compared to the healthy control group . In this study, SCD patho

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Publication Date
Sat Jun 25 2022
Journal Name
International Journal Of Drug Delivery Technology
Evaluation of IL17A, FGF21 and CXC12 in Post-menopause Iraqi Sample with Osteoporosis and Osteopenia
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Osteoporosis (OP) is a systemic skeletal disorder that is characterized by reduced bone mass and micro-architectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture. The most frequent osteoporotic fractures are fractures of the hip, wrist, and spine. The exact causes of OP are still unknown; several factors contribute to the disorder. Subjects and Methods: This study consists of patient groups, this group (Group A) was composed of 80 postmenopausal women with OP and osteopenia and the patient group was subdivided into two group; First group (GroupA1) was composed of 50 postmenopausal women with OP and the second group (Group A2) composed of (30) Postmenopausal Women with oste

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Publication Date
Tue Sep 05 2017
Journal Name
Cell Adhesion & Migration
Periodontal pathogens promote epithelial-mesenchymal transition in oral squamous carcinoma cells <i>in vitro</i>
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Publication Date
Mon Jan 01 2024
Journal Name
Journal Of Research In Pharmacy
Phytochemical constituents of ethyl acetate fraction of both roots and leaves of Sansevieria triafasciata cultivated in Iraq and assessment of its anti-proliferative effect on breast cancer cell line
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Publication Date
Wed Dec 05 2018
Journal Name
Italian Journal Of Gynaecology & Obstetrics
Prediction of Fetal Lung Maturity by Ultrasonic Thalamic Echogenicity and Ossification Centers of Fetal Femur and Tibia
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