2. Epigenetics
  3. DNA Methyltransferase
  4. NV914

NV914 是一种 FTSJ1 (色氨酸 tRNA 特异性 2'-O-甲基转移酶) 抑制剂，能够抑制 FTSJ1 甲基转移酶活性，诱导提前终止密码子的翻译通读，使携带无义突变的基因合成全长蛋白。NV914 属于翻译通读诱导化合物 (TRID)，在体外系统中对无义突变具有翻译通读活性，且不诱导天然终止密码子通读，可恢复 CFTR 蛋白表达。NV914 在小鼠体内表现出良好的急性口服耐受性，健康风险较低，安全性良好。NV914 可用于囊性纤维化、Shwachman-Diamond 综合征的相关研究。

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NV914

NV914 Chemical Structure

CAS No. : 2341941-41-9

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NV914 相关抗体

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  • 生物活性

  • 纯度 & 产品资料

  • 参考文献

生物活性

NV914 is an inhibitor of FTSJ1 (tryptophan tRNA-specific 2'-O-methyltransferase) that inhibits the methyltransferase activity of FTSJ1, induces translational readthrough of premature termination codons, and enables genes carrying nonsense mutations to synthesize full-length proteins. NV914 belongs to translational readthrough-inducing compounds (TRIDs). NV914 exhibits translational readthrough activity against nonsense mutations in in vitro systems, does not induce readthrough of natural termination codons, and restores CFTR protein expression. NV914 shows favorable acute oral tolerance in mice, with low health risks and good safety profiles. NV914 is applicable to research related to cystic fibrosis and Shwachman-Diamond syndrome[1][2][3].
体外研究
(In Vitro)

NV914 (3-48 μM；24 h) 不会在 HCT116 细胞中诱导 NTC 通读，因为在联合多柔比星 (Doxorubicin) 处理后未检测到更高分子量的p53条带[1]。
NV914 (3-48 μM；24 h) 处理联合阿霉素后，不会改变 HCT116 细胞中 p53 的核定位[1]。
NV914 (3-48 μM；24 h) 处理联合 Doxorubicin 后，不会损伤 HCT116 细胞中的 p53 功能 (以p21 mRNA 表达水平为检测指标)[1]。
NV914 (12-100 μM；24 或 72 h) 不会在 16HBE 细胞中诱导 NTC 通读，因为处理后未检测到更高分子量的 Cys-C 或 β2M 条带[1]。
NV914 (6-24 μM；24 h) 可诱导转染 pFLuc190UGA 的 HeLa 细胞中 UGA 提前终止密码子的通读，而该活性会被 FTSJ1 过表达抵消[3]。
NV914 (12 μM; 24 h) 可诱导 IB3.1 囊性纤维化细胞中 W1282X UGA 提前终止密码子的通读，且该活性会因FTSJ1过表达而降低[3]。

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

NV914 相关抗体:

Western Blot Analysis[1]

Cell Line: HCT116 colon cancer cells
Concentration: 3-48 μM
Incubation Time: 24 h
Result: Detected a slight decrease in p53 protein levels in cells treated with NV914 and Doxorubicin compared to Doxorubicin-only samples; showed no p53 bands with higher molecular weights (indicative of natural termination codon [NTC] readthrough).

Immunofluorescence[1]

Cell Line: HCT116 colon cancer cells
Concentration: 3-48 μM
Incubation Time: 24 h
Result: Localized p53 fluorescent signal in the cell nuclei in all cell samples treated with Doxorubicin and NV914; observed no significant change in p53 nuclear localization.

Western Blot Analysis[1]

Cell Line: 16HBE human bronchial epithelial cells
Concentration: 12-100 μM (24 h treatment); 12-100 μM (72 h treatment, refreshed every 24 h)
Incubation Time: 24 h; 72 h (treatments refreshed every 24 h)
Result: Detected no bands corresponding to higher molecular weight forms of Cys-C or β2M in cells treated with NV914 for 24 or 72 h.
体内研究
(In Vivo)

NV914 (2000 mg/kg；经口给药；单剂量) 在健康 C57BL/6 小鼠中耐受性良好，仅出现暂时性毒性体征且无显著器官损伤，因此被归类为 GHS category 5 (低健康风险)[2]。

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: C57BL/6 (both sexes, 6-8 weeks old, weight 18±4 g)[2]
Dosage: 2000 mg/kg
Administration: p.o.; single dose
Result: Observed no mortality within 14 days.
Recorded hypoactivity in 5 of 6 treated mice, hyperactivity and abdominal pain in 4 of 6, tremors and convulsions in 3 of 6, itching and scratching in 2 of 6; resolved all toxicity signs within 3 h post-treatment.
Detected no significant difference in body weight growth patterns compared to controls.
Found no significant morphological alterations in analyzed organs, except for a slight tendency to maturation disturbance of neutrophil granulocytes and weak expansion of erythroid lineage in two bone marrow samples.
分子量

445.18

Formula

C15HF10N3O2
CAS 号
运输条件

Room temperature in continental US; may vary elsewhere.
储存方式

Please store the product under the recommended conditions in the Certificate of Analysis.
纯度 & 产品资料
参考文献

NV914 相关分类

  • 摩尔计算器

  • 稀释计算器

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Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

NV9142341941-41-9NV 914NV-914DNA MethyltransferaseDNMTsDNA MTasestryptphan tRNA-specific 2'-O-methyltransferaseshwachman-diamond syndromeHeLa cellsmurine modelsHCT116 cellsFTSJ1CFTR proteincystic fibrosispremature termination codonsnatural termination codonsInhibitorinhibitorinhibit

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