Фамилия, имя переводчика ________________________
Задание:
Переведите приведенные ниже фрагменты, вводя перевод в соответствующий столбец. Если тематика фрагмента кажется вам совсем незнакомой, воздержитесь от его перевода. Однако не избегайте перевода понятных вам фрагментов: чем больше фрагментов вы переведете, тем проще нам будет предложить вам работу. Как минимум в тесте должны быть переведены любые два фрагмента.
Символы XXX, YYY, ZZZ, NNN и KKK заменяют некоторые названия, опущенные из соображений конфиденциальности. Эти символы применяются последовательно (то есть означают одно и то же) в рамках одного фрагмента. В разных фрагментах одинаковой меткой могут обозначаться разные названия.
Некоторые аббревиатуры в тексте поясняются в сносках. Переводить текст сносок не нужно.
Оригинал | Перевод |
I | |
XXX is a novel HCV nonstructural protein (NS)5B polymerase nucleotide inhibitor that has displayed potent in vitro inhibition of HCV replicon ribonucleic acid (RNA) replication in vitro. | |
XXX is a nucleotide prodrug of 2’-deoxy-2’-fluoro-2’-C-methyluridine monophosphate that is converted to the active uridine analog triphosphate form (YYY) within the hepatocyte. | |
YYY is incorporated by the HCV NS5B polymerase during HCV RNA replication, and acts to inhibit RNA replication via chain termination. | |
Because YYY targets a catalytic site that is highly conserved across genotypes 1 through 6, XXX has pan-genotypic HCV activity. | |
II | |
XXX has three polymorphs, designated Form-α, Form-β and Form-γ. | |
No hydrate or solvate has been observed. | |
Form-γ is the most stable of the three polymorphs with the highest melting point ranging from 161 to 165 °C. | |
Form-γ was used in the Phase 3 clinical studies and is the only form isolated from the commercial synthetic process. | |
The anhydrous crystalline Form-γ is physically and chemically stable in solid state when exposed to heat, humidity, and light. | |
III | |
A commercial bioanalytical method for determination of XXX in human urine was developed and validated at ZZZ (Newark, DE, USA). | |
This method involved the protein precipitation extraction of XXX and its internal standard (YYY) from human urine followed by LC/MS/MSi with positive ionization (ZZZ validation report NNN). | |
Calibration curves for XXX ranged from 500 (LLOQii) to 200,000 ng/mL. | |
Standards, quality control solutions, blank matrix, and study samples (as applicable) were prepared according to the validated methods. | |
The fully validated bioanalytical method was used to determine concentrations of XXX in human urine samples collected in Study KKK. | |
All samples were analyzed within the time frame supported by the LTSSiii data. | |
IV | |
Nucleoside inhibitors play central roles in antiviral therapy; however, some nucleoside inhibitors have been associated with toxicities related to inhibition of host DNA and RNA polymerases. | |
Furthermore, inhibition of mitochondrial function has been proposed as a mechanism for toxicity of many agents. | |
This is true for some antiviral and antibacterial drugs, many of which are designed to inhibit viral/bacterial replication and can have similar off-target effects on mitochondrial DNA or RNA synthesis. | |
Consistent with the lack of inhibition of the mitochondrial DNA POL г, XXX did not deplete mitochondrial DNA following treatment of the liver cell line Hep G2 for 10 days at the highest concentration tested (20 µM). |
i LC/MS/MS — liquid chromatography/tandem mass spectrometry
ii LLOQ — lower limit of quantitation
iii LTSS — long-term storage stability
