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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
Mon Mar 03 2014
Journal Name
Journal Of Baghdad College Of Dentistry
Stem Cells a Novel Approach to Periodontal Regeneration: A Review of Literature
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Publication Date
Fri Jul 01 2016
Journal Name
Al–bahith Al–a'alami
The Discourse of the Absent Woman Novel for Mahdi Issa Al-Saqr
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The semiotic trend of recent monetary trends task that took a wide range of attention of critics and readers alike, especially after the deployment, which accompanied him after widespread acts critic Grimas and powers applicable to the literary texts and is thus expanded its care circle, hence the choice of the novel (absent) woman Iraqi novelist (Mahdi ‘Issa falcon) model to be applied to the study chose to be a semiotic approach through the use of procedural mechanisms for its critical tool (Paris School of semiotics), cash and views of its founder critic Grimas.The research in the introduction and pave came we made it a vision for literary semiotic and its impact trend in cash and cash is and what it desire to clarify some poked suc

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Publication Date
Thu Aug 03 2023
Journal Name
Cogent Arts &humanities
An Ecostylistic Analysis of Selected Extracts from Michael Punke’s Novel The Revenant
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Publication Date
Wed Feb 15 2017
Journal Name
School Of Engineering
Development of novel demountable shear connectors for precast steel-concrete composite bridges
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Two novel demountable shear connectors for precast steel-concrete composite bridges are presented. The connectors use high-strength steel bolts, which are fastened to the steel beam with the aid of a special locking configuration that prevents slip of bolts within their holes. Moreover, the connectors promote accelerated construction and overcome typical construction tolerances issues of precast structures. Most importantly, the connectors allow bridge disassembly, and therefore, can address different bridge deterioration scenarios with minimum disturbance to traffic flow, i.e. (1) precast deck panels can be rapidly uplifted and replaced; (2) connectors can be rapidly removed and replaced; and (3) steel beams can be replaced, while precast

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Publication Date
Mon Jun 09 2025
Journal Name
Journal Of Discrete Mathematical Sciences And Cryptography
A novel improvement of skew tent map for generating Pseudo random numbers
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An encryption system needs unpredictability and randomness property to maintain information security during transmission and storage. Although chaotic maps have this property, they have limitations such as low Lyapunov exponents, low sensitivity and limited chaotic regions. The paper presents a new improved skewed tent map to address these problems. The improved skew tent map (ISTM) increases the sensitivity to initial conditions and control parameters. It has uniform distribution of output sequences. The programs for ISTM chaotic behavior were implemented in MATLAB R2023b. The novel ISTM produces a binary sequence, with high degree of complexity and good randomness properties. The performance of the ISTM generator shows effective s

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Publication Date
Sat Sep 01 2018
Journal Name
King's College London
A novel sol-gel silica formulation for management of methadone hydrochloride abuse
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Introduction: Methadone hydrochloride (MDN) is an effective pharmacological substitution treatment for opioids dependence, adopted in different countries as methadone maintenance treatment (MMT) programmes. However, MDN can exacerbate the addiction problem if it is abused and injected intravenously, and the frequent visits to the MMT centres can reduce patient compliance. The overall aim of this study is to develop a novel extended-release capsule of MDN using the sol-gel silica (SGS) technique that has the potential to counteract medication-tampering techniques and associated health risks and reduce the frequent visits to MMT centres. Methods: For MDN recrystallisation, a closed container method (CCM) and hot-stage method (HSM) were conduc

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Publication Date
Wed Aug 28 2024
Journal Name
Mesopotamian Journal Of Cybersecurity
A Novel Anomaly Intrusion Detection Method based on RNA Encoding and ResNet50 Model
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Cybersecurity refers to the actions that are used by people and companies to protect themselves and their information from cyber threats. Different security methods have been proposed for detecting network abnormal behavior, but some effective attacks are still a major concern in the computer community. Many security gaps, like Denial of Service, spam, phishing, and other types of attacks, are reported daily, and the attack numbers are growing. Intrusion detection is a security protection method that is used to detect and report any abnormal traffic automatically that may affect network security, such as internal attacks, external attacks, and maloperations. This paper proposed an anomaly intrusion detection system method based on a

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Publication Date
Thu Oct 26 2023
Journal Name
International Journal Of Environment And Waste Management
Novel Poly (3-hydroxybutyrate) production using Bacillus subtilis NG220 and watermelon derived substrates
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Poly (3-hydroxybutyrate) (PHB) is a typical microbial bio-polyester reserve material; known as “green plastics”, which produced under controlled conditions as intracellular products of the secondary metabolism of diverse gram-negative/positive bacteria and various extremophiles archaea. Although PHB has properties allowing being very attractive, it is too expensive to compete with conventional and non-biodegradable plastics. Feasibility of this research to evaluate the suitability of using a watermelon-derived media as an alternative substrate for PHB synthesis under stress conditions was examined. Results, include the most nutrients extraction, indicated that the watermelon seeds contain a high content of nutrients makes them a promisi

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Publication Date
Wed Aug 28 2024
Journal Name
Mesopotamian Journal Of Cybersecurity
A Novel Anomaly Intrusion Detection Method based on RNA Encoding and ResNet50 Model
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Cybersecurity refers to the actions that are used by people and companies to protect themselves and their information from cyber threats. Different security methods have been proposed for detecting network abnormal behavior, but some effective attacks are still a major concern in the computer community. Many security gaps, like Denial of Service, spam, phishing, and other types of attacks, are reported daily, and the attack numbers are growing. Intrusion detection is a security protection method that is used to detect and report any abnormal traffic automatically that may affect network security, such as internal attacks, external attacks, and maloperations. This paper proposed an anomaly intrusion detection system method based on a

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Publication Date
Mon Jan 01 2024
Journal Name
Journal Of Industrial And Engineering Chemistry
Petroleum refinery wastewater treatment using a novel combined electro-Fenton and photocatalytic process
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