NMDI14
目录号 : GC32744
NMDI14是一种无义介导的RNA衰变(NMD)抑制剂。
Cas No.:307519-88-6
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
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Cell experiment: |
To assess viability cells are cultured in 6 well dishes and incubated with DMSO, G418, NMDI alone or G418 with NMDI together for the indicated hours. After incubations, cells and media are collected and cells viability is measured. To assess cell proliferation U2OS, Hela and BJ-htert cells are cultured in 6 well plates and, after 24 hrs, treated with NMDI14 for 0, 24, 48 and 72hrs. The cells are collected and viable cells are counted by using the Countess Automated Cell Counter[1]. |
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References: [1]. Martin L, et al. Identification and characterization of small molecules that inhibit nonsense-mediated RNA decay and suppress nonsense p53 mutations. Cancer Res. 2014 Jun 1;74(11):3104-1 |
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NMDI14 is a nonsense mediated RNA decay (NMD) inhibitor.
NMDI14 is a nonsense mediated RNA decay (NMD) inhibitor. Treating cells with NMDI14 for 6 hours leads to an increase of PTC 39 β globin to 12%, a relative four-fold increase that, if resulting in biologically active hemoglobin, would be sufficient to ameliorate the clinical symptoms of thalassemia. Three days of treatment with NMDI14 results in no decrease in cell counts, demonstrating that the pharmacological inhibition of NMD can be achieved without subtle changes in proliferation. 941 genes are increased >1.5 fold with NMDI14. The treatment of N417 cells with NMDI14 for 6 hours leads to a steady state expression of p53 similar to that seen in U2OS cells. NMDI14 significantly increases the stability of PTC mutated p53 mRNA in N417 cells, without altering the stability of wild-type p53 in NMDI treated U2OS cells[1].
[1]. Martin L, et al. Identification and characterization of small molecules that inhibit nonsense-mediated RNA decay and suppress nonsense p53 mutations. Cancer Res. 2014 Jun 1;74(11):3104-1
| Cas No. | 307519-88-6 | SDF | |
| Canonical SMILES | O=C(C1=C(NC(CC2NC3=C(C=C(C)C(C)=C3)NC2=O)=O)SC(C)=C1C)OCC | ||
| 分子式 | C21H25N3O4S | 分子量 | 415.51 |
| 溶解度 | DMSO : ≥ 25 mg/mL (60.17 mM) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.4067 mL | 12.0334 mL | 24.0668 mL |
| 5 mM | 0.4813 mL | 2.4067 mL | 4.8134 mL |
| 10 mM | 0.2407 mL | 1.2033 mL | 2.4067 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Decreased mRNA and protein stability of W1282X limits response to modulator therapy
J Cyst Fibros 2019 Sep;18(5):606-613.PMID:30803905DOI:PMC6706327
Background: Cell-based studies have shown that W1282X generates a truncated protein that can be functionally augmented by modulators. However, modulator treatment of primary cells from individuals who carry two copies of W1282X generates no functional CFTR. To understand the lack of response to modulators, we investigated the effect of W1282X on CFTR RNA transcript levels. Methods: qRT-PCR and RNA-seq were performed on primary nasal epithelial (NE) cells of a previously studied individual who is homozygous for W1282X, her carrier parents and control individuals without nonsense variants in CFTR. Results: CFTR RNA bearing W1282X in NE cells shows a steady-state level of 4.2 ± 0.9% of wild-type (WT) CFTR RNA in the mother and 12.4 ± 1.3% in the father. NMDI14, an inhibitor of nonsense-mediated mRNA decay (NMD), restored W1282X mRNA to almost 50% of WT levels in the parental NE cells. RNA-seq of the NE cells homozygous for W1282X showed that CFTR transcript level was reduced to 1.7% of WT (p-value: 4.6e-3). Negligible truncated CFTR protein was generated by Flp-In 293 cells stably expressing the W1282X EMG even though CFTR transcript was well above levels observed in the parents and proband. Finally, we demonstrated that NMD inhibition improved the stability and response to correctors of W1282X-CFTR protein expressed in the Flp-In-293 cells. Conclusion: These results show that W1282X can cause substantial degradation of CFTR mRNA that has to be addressed before efforts aimed at augmenting CFTR protein function can be effective.