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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 May 01 2026
Journal Name
2026 Xxix International Conference On Soft Computing And Measurements (scm)
Hierarchical Multi-Stage Intrusion Detection with Feature Inheritance and Prediction Verification
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One of the challenges faced by traditional intrusion detection systems based on machine learning or deep learning is instability when dealing with unbalanced network traffic, leading to failure in detecting certain attacks (minority classifications). Additionally, they struggle with multi-stage attacks, resulting in an increase in false alarms. This paper presents a hierarchical intrusion detection system supported by a Prediction Verification Layer (PVL) and a Feature Inheritance Mechanism (FIM). Where PVL contributes to documenting the system’s final decision and increasing sensitivity to minority attacks, FIM also helps in inheriting features from previous layers and correcting errors as much as possible. Additionally, it allows for ad

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Publication Date
Tue Dec 30 2008
Journal Name
Al-kindy College Medical Journal
Clinical Evaluation of the Levels of CEA,CA15-3 and AlphaFeto Protein in Malignant and Benign Pleural Effusion
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Background: Pleural effusion is a common clinical
problem.
Objective: The aim of the study was to evaluate the
diagnostic utility of Carcino embryonic antigen
(CEA), CA 15- 3, and alpha-feto protein ( AFP ) as
a tumor markers in serum and pleural effusion and
evaluate the value of combining them as a diagnostic
tools that are complementary to cytology in the
diagnosis of malignancies .
Methods: Forty patients (18 malignant and 22 benign
pleural effusion) were included in this study .The
serum and effusion levels of CEA, CA 15 – 3 and
AFP were measured using immunoradiometric assay
Results: from the 40 effusions studied 26 were
exudates and 14 were transudates. The level of
pleural effusions

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Publication Date
Tue Dec 15 2020
Journal Name
Journal Of Baghdad College Of Dentistry
Coated stainless steel archwires' discoloration measured by computerized system (An in-vitro study)
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Background: Aesthetic archwires are used to overcome the aesthetic problems of stainless steel wires but the color of the coating layer can be changed with time when exposed to oral environments. The aim of this study was to evaluate the degree of color change of different aesthetic archwires from different companies under different coloring solutions. Materials and Methods: One hundred fifty samples of coated archwires from three companies (Highland, G&H and Dany) were immersed in 5 solutions (artificial saliva, turmeric, tea, coffee and Miranda) to evaluate the degree of color changes after 7, 14 and 21 days using visible spectrophotometer. Data were collected and analyzed using one way ANOVA and post hoc Tukey’s tests. Resu

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Publication Date
Fri Feb 08 2019
Journal Name
Iraqi Journal Of Laser
Urinary Tract Stones Fragmentation using (2100 nm) Holmium: YAG Laser: (In vitro Analysis)
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Urinary stones are one of the most common painful disorders of the urinary system. Four new technologies have transformed the treatment of urinary stones: Electrohydraulic lithotripsy, ultrasonic lithotripsy, extracorporeal shock wave lithotripsy, and laser lithotripsy.The purpose of this study is to determine whether pulsed holmium laser energy is an effective method for fragmenting urinary tract stones in vitro, and to determine whether stone composition affects the efficacy of holmium laser lithotripsy. Human urinary stones of known composition with different sizes, shapes and colors were used for this study. The weight and the size of each stone were measured. The surgical laser system which used in our study is Ho:YAG laser(2100nm)

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Publication Date
Fri Feb 08 2019
Journal Name
Iraqi Journal Of Laser
Human Skin WoundWelding Using 980 nm Diode Laser: an in Vitro Experimental Study
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Laser assisted skin wound closure offers many distinct advantages over conventional closure
techniques. The objective of this in vitro experimental study, carried out at the Institute of Laser for
Postgraduate Studies/Baghdad University, was to determine the effectiveness of 980 nm diode laser in
welding of human skin wounds. Multiple 3-4 cm long full thickness incisions in a specimen of human
skin obtained from the discarded panniculus of an Abdominoplasty operation were tried to be laser
welded using a 4 mm spot diameter laser beam from a 980 nm diode laser at different laser parameters
and modes of action. The tensile strength at the weld site was analyzed experimentally. Although laser
assisted wound welding did

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Publication Date
Sat Sep 15 2018
Journal Name
Journal Of Baghdad College Of Dentistry
Evaluation of the efficacy of ultrasound in the diagnosis of cervical lymphadenopathy
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Background: Cervical lymph nodes are prone to involved by a number of pathologic processes. They are common sites for lymphoma, metastasis, and reactive enlargement in a number of conditions. Aims of the study:-Clinical evaluation of patients with cervical lymphadenopathy. Differentiation between benign and malignant lymph nodes by means of ultra sounds (US) and Correlate the US findings with cytological and/or histopathological findings of cervical lymph nodes. Subjects, Materials and Methods:-The present study was carried out over a period of 6 months and included 81 patients of different age groups presenting with cervical lymphadenopathy. Each patient was examined clinically, then comprehensive sonographic examination of the neck for

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Crossref
Publication Date
Mon Apr 04 2022
Journal Name
Journal Of Research In Medical And Dental Science
Efficacy of Varnishes with: Bioactive Glass, Recaldent Technology and Silver Diamine Fluoride in Comparison with Sodium Fluoride on Tooth Surface Micro-hardness (an In Vitro Study)
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Efficacy of Varnishes with: Bioactive Glass, Recaldent Technology and Silver Diamine Fluoride in Comparison with Sodium Fluoride on Tooth Surface Micro-hardness (an In Vitro Study)

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Publication Date
Wed Apr 13 2022
Journal Name
International Journal Of Medical Sciences
Evaluation of the Levels of Erythropoietin and Some Haehematological Parameters in Patients with History of Haemodialysis and Non- haemodialysis
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Publication Date
Fri Jan 24 2025
Journal Name
Plos One
Assessment of the bypass of obturation materials beyond fractured instruments after using different obturation techniques in simulated curved canals (An in-vitro study)
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This study evaluated the extent to which obturation materials bypass fractured endodontic instruments positioned in the middle and apical thirds of severely curved simulated root canals using different obturation techniques. Sixty resin blocks with simulated root canals were used, each with a 50° curvature, a 6.5 mm radius of curvature, and a length of 16.5 mm, prepared to an ISO #15 diameter and taper. Canals were shaped using ProTaper Universal files (Dentsply Maillefer) attached to an X-smart Plus endo motor (Dentsply), set at 3.5 Ncm torque and 250 rpm, up to size S2 at working length. To simulate fractures, F2 and F3 files were weakened 3 mm from the tip, then twisted to break in the apical and middle sections of the canal, re

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Publication Date
Fri Sep 01 2023
Journal Name
Journal Of Education And Scientific Studies
Studying the effect of laser stress in combination with mannitol on some morphological parameters of cabbage (Brassica oleracea var L. capitata) In vitro
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