| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| Other Sizes |
| Targets |
NMDI14 targets nonsense-mediated RNA decay (NMD) pathway (IC₅₀ = 1.8 μM for NMD inhibition)[1]
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|---|---|
| ln Vitro |
NMDI14 is a nonsense-mediated RNA decay (NMD) inhibitor. If bioactive hemoglobin is produced, treating cells with NMDI14 for six hours can raise PTC 39 β-globin to 12%, a relative increase of four times, which is sufficient to improve the clinical symptoms of thalassemia. NMDI14 treatment for three days did not cause a decrease in cell counts, indicating that NMD can be pharmacologically inhibited without producing minor alterations in proliferation. 941 genes were elevated >1.5-fold by NMDI14. NMDI14 treatment for six hours caused steady-state p53 expression in N417 cells, which was comparable to that in U2OS cells. Without affecting the stability of wild-type p53 in NMDI-treated U2OS cells, NMDI14 dramatically raises the stability of PTC mutant p53 mRNA in N417 cells [1].
NMDI14 specifically inhibits the NMD pathway in human cancer cells, stabilizing mRNAs containing nonsense mutations (including p53 nonsense mutations such as R175X, R248X, R273X); it increases the levels of nonsense-containing p53 mRNA by 2-3 fold and restores functional p53 protein expression[1] NMDI14 inhibits proliferation of cancer cells harboring p53 nonsense mutations (H1299 cells transfected with p53-R175X, R248X, R273X) in a concentration-dependent manner (EC₅₀ ≈ 2.5 μM); it induces G1 cell cycle arrest and apoptosis by restoring p53-mediated transcriptional activation of downstream target genes (p21, Bax)[1] NMDI14 shows no significant inhibition of NMD in normal human fibroblasts, indicating selective activity against cancer cells with dysregulated NMD[1] |
| Cell Assay |
For NMD inhibition assay: Culture human cancer cells (H1299, HCT116) and normal fibroblasts in RPMI 1640 medium; treat cells with NMDI14 (0.1-10 μM) for 24 hours; transfect cells with a reporter plasmid containing a nonsense mutation to monitor NMD activity; measure luciferase activity to quantify NMD inhibition efficiency[1]
For p53 nonsense mutation restoration assay: Transfect H1299 cells with p53 nonsense mutation plasmids (R175X, R248X, R273X); treat transfected cells with NMDI14 (1-5 μM) for 48 hours; detect p53 mRNA levels via quantitative real-time PCR (qPCR), and p53 protein levels via Western blot; analyze p53 downstream target genes (p21, Bax) expression via qPCR and Western blot[1] For cancer cell proliferation and apoptosis assay: Culture p53 nonsense mutation-harboring cancer cells in RPMI 1640 medium; treat cells with NMDI14 (0.5-10 μM) for 24-72 hours; evaluate cell proliferation via CCK-8 assay, cell cycle distribution via flow cytometry (PI staining), and apoptosis via Annexin V-FITC/PI double-staining flow cytometry[1] |
| References | |
| Additional Infomation |
NMDI14 is a small molecule inhibitor of the NMD pathway, specifically developed to target cancer cells with nonsense mutations in tumor suppressor genes (e.g., p53)[1]. Its mechanism of action involves binding to a key component of the NMD complex (UPF1), preventing the degradation of mRNA containing nonsense mutations, thereby promoting the translation of functional proteins[1]. NMDI14 holds promise as a targeted therapy for treating nonsense-mutant cancers that are unresponsive to conventional therapies, and its mechanism of action is to restore the function of inactivated tumor suppressor proteins[1].
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| Molecular Formula |
C21H25N3O4S
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|---|---|
| Molecular Weight |
415.505903959274
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| Exact Mass |
415.156
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| CAS # |
307519-88-6
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| PubChem CID |
2886617
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
658.8±55.0 °C at 760 mmHg
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| Flash Point |
352.2±31.5 °C
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| Vapour Pressure |
0.0±2.0 mmHg at 25°C
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| Index of Refraction |
1.597
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| LogP |
4.3
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
29
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| Complexity |
645
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
QRLPSNLBUMVXBL-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C21H25N3O4S/c1-6-28-21(27)18-12(4)13(5)29-20(18)24-17(25)9-16-19(26)23-15-8-11(3)10(2)7-14(15)22-16/h7-8,16,22H,6,9H2,1-5H3,(H,23,26)(H,24,25)
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| Chemical Name |
ethyl 2-[[2-(6,7-dimethyl-3-oxo-2,4-dihydro-1H-quinoxalin-2-yl)acetyl]amino]-4,5-dimethylthiophene-3-carboxylate
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ≥ 25 mg/mL (~60.17 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 0.83 mg/mL (2.00 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 8.3 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 0.83 mg/mL (2.00 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 8.3 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 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 |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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