Background: Trastuzumab is a blockbuster monoclonal antibody that has revolutionized the treatment of HER2-positive breast and gastric cancers. With the increasing availability of biosimilar monoclonal antibodies in clinical practice, independent verification of biosimilarity using products sampled from a real-world supply chain is important to assure clinicians and the patients to use these products confidently. Objective: The aim of this study is to assess the biosimilarity of AryoTrust, a trastuzumab biosimilar, in comparison with the reference product Herceptin. AryoTrust and Herceptin products were randomly withdrawn from Iraqi hospitals to reflect medicines administered in real clinical settings. Methods: AryoTrust and Herceptin were compared using an extensive set of orthogonal analytical techniques which included SDS-PAGE, ion-exchange chromatography, capillary isoelectric focusing, peptide mapping, N-glycan profiling, circular dichroism, differential scanning calorimetry, and surface plasmon resonance. In addition to these teste, functional comparability was also tested using an HER2-dependent cell-based proliferation inhibition bioassay. Results: The results showed that both products have highly comparable profiles in all assessed attributes. The analysis showed similar molecular integrity and purity, identical primary structure, comparable charge heterogeneity, similar isoelectric points (pI) of the main isoform, close glycosylation patterns (mainly, by core-fucosylated complex-type glycans), similar higher-order structural features, and thermal stability. The receptor binding studies exhibited comparable binding affinities with Fcγ receptors and FcRn. Finally, the cell-based bioassay revealed comparable dose–response curves with similar EC50 values and relative potency. Conclusions: The integrated analytical and functional data support the biosimilarity of AryoTrust to the reference product Herceptin, which has been marketed and used in Iraq. This study provides real-world scientific evidence supporting confidence in the quality and comparability of this trastuzumab biosimilar and reduces any doubt in the product and at the same time emphasizes the value of independent post-marketing biosimilarity assessments.
Compound 4-(((6-amino-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazin-3-yl)methoxy)methyl)- 2,6-dimethoxyphenol (6) was synthesized by multi steps. The corresponding acetonitrile thioalkyl (7) was cyclized by refluxing with acetic acid to afford 4-(((6-amino-7H-[1,2,4]triazolo[3,4- b][1,3,4]thiadiazin-3-yl)methoxy)methyl)-2,6-dimethoxyphenol (8). Two new series of 4-(((6-(3- (4-aryl)thioureido)-7H-[1,2,4]triazolo[3,4-b][1,3,4] thiadiazin-3-yl)methoxy)methyl)-2,6- dimethoxyphenol (9a-c) and of 4-(((6-(substitutedbenzamido)7H-[1,2,4]triazolo[3,4- b][1,3,4]thiadiazin-3-yl)methoxy)methyl)-2,6-dimethoxyphenol (10a-c) were synthesized as new derivatives for fused 1,2,4-trizaole-thiadiazine(8). The antioxidants of newly compounds were evaluated by DPPH
... Show MoreCompound 4-(((6-amino-7H-[1, 2, 4] triazolo [3, 4-b][1, 3, 4] thiadiazin-3-yl) methoxy) methyl)-2, 6-dimethoxyphenol (6) was synthesized by multi steps. The corresponding acetonitrile thioalkyl (7) was cyclized by refluxing with acetic acid to afford 4-(((6-amino-7H-[1, 2, 4] triazolo [3, 4-b][1, 3, 4] thiadiazin-3-yl) methoxy) methyl)-2, 6-dimethoxyphenol (8). Two new series of 4-(((6-(3-(4-aryl) thioureido)-7H-[1, 2, 4] triazolo [3, 4-b][1, 3, 4] thiadiazin-3-yl) methoxy) methyl)-2, 6-dimethoxyphenol (9a-c) and of 4-(((6-(substitutedbenzamido) 7H-[1, 2, 4] triazolo [3, 4-b][1, 3, 4] thiadiazin-3-yl) methoxy) methyl)-2, 6-dimethoxyphenol (10a-c) were synthesized as new derivatives for fused 1, 2, 4-trizaole-thiadiazine (8). The antioxidant
... Show MoreThe present article discusses innovative word-formation processes in Internet texts, the emergence of new derivative words, new affixes, word-formation models, and word-formation methods. Using several neologisms as an example, the article shows both the possibilities of Internet word-making process and the possibilities of studying a newly established work through Internet communication. The words selected for analysis can be attributed to the keywords of the current time. (In particular, the words included in the list of "Words of 2019") there are number of words formed by the suffix method, which is the traditional method of the Russian word formation. A negation of these words is usually made thro
... Show MoreIn this study new derivatives of O-[2-{''2-Substituted Aryl (''1,''3,''4 thiadiazolyl) ['3,'4-b]-'1,'2,'4- Triazolyl]-Ethyl]-p- chlorobenzald oxime (6-11)have been synthesized from the starting material p-chloro – E- benzaldoxime 1.Compound 2 was synthesized by the reaction of p-chloro – E- benzaldoxime with ethyl acrylate in basic medium. Refluxing compound 2 with hydrazine hydrate in ethanol absolute afforded 3. Derivative 4 was prepared by the reaction of 3 with carbon disulphide, treated of compound 4 with hydrazine hydrate gave 5. The derivatives (6-11) were prepared by the reaction of 5 with different substitutesof aromatic acids. The structures of these compounds were characterized from their melting points, infrared spectroscopy
... Show MoreThe present study attempts to identify some of the differences between the skull bones of two species Cyprinus carpio and Carassius carassius, which belong to the Cyprinidae family. The study is a taxonomic diagnostic study between the two species which are considered local fish abundant in the Iraqi aquatic environment
Background: L. sativum, are traditionally used for the treatment of various diseases and thought to have medicinal value. Isolates from many part of the world is now multidrug resistant. Therefore, there is an urgent need to look for and test an alternative herbal drug.
Objective: The present study aimed to evaluate the antibacterial activity of L. Sativum seed extract against multi drug resistant (MDR) and sensitive Pseudomonas aeruginosa clinical isolates.
Subjects and Methods: An ethanolic and aqueous stock extracts were prepared from L. sativum seed plant then serial dilutions were prepared and the obtained concentrations (50, 25, 12.5 and 6.2 mg/ml) were tested against 30 multidrug-resistan
... Show MoreSildenafil, tadalafil, and vardenafil are phosphodiesterase type 5 enzyme (PDE-5) inhibitors used for the treatment of male erectile dysfunction. This present study aims to investigate 55 herbal products indicated for men’s sexual health from the Malaysian market for adulteration of PDE-5 inhibitors and analogues. The screening and identification of 20 PDE-5 inhibitors and analogues in herbal products of various forms (powder, capsules, tablets, and pastels) were conducted using gas chromatography–electron impact-mass spectrometer (GC-EI-MS). The analysis has shown that 19 herbal products were adulterated with PDE-5 inhibitors and analogues. Unique ion fragmentations and the presence of molecular
... Show MoreWe report here an innovative feature of green nanotechnology-focused work showing that mangiferin—a glucose functionalized xanthonoid, found in abundance in mango peels—serves dual roles of chemical reduction and in situ encapsulation, to produce gold nanoparticles with optimum in vivo stability and tumor specific characteristics. The interaction of mangiferin with a Au-198 gold precursor affords MGF-198AuNPs as the beta emissions of Au-198 provide unique advantages for tumor therapy while gamma rays are used for the quantitative estimation of gold within the tumors and various organs. The laminin receptor specificity of mangiferin affords specific accumulation of therapeutic payloads of this new therapeutic agent within prostate tumors
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