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Purity: ≥98%
ML414 (also known NGI-1) is a novel and cell-permeable inhibitor of oligosaccharyltransferase (OST), which is a hetero-oligomeric enzyme that exists in multiple isoforms and transfers oligosaccharides to recipient proteins. ML414 was identified from a cell-based high-throughput screen and lead-compound-optimization campaign. In non-small-cell lung cancer cells, NGI-1 blocks cell-surface localization and signaling of the epidermal growth factor receptor (EGFR) glycoprotein, but selectively arrests proliferation in only those cell lines that are dependent on EGFR (or fibroblast growth factor, FGFR) for survival. In these cell lines, OST inhibition causes cell-cycle arrest accompanied by induction of p21, autofluorescence, and cell morphology changes, all hallmarks of senescence. These results identify OST inhibition as a potential therapeutic approach for treating receptor-tyrosine-kinase-dependent tumors and provides a chemical probe for reversibly regulating N-linked glycosylation in mammalian cells.
| Targets |
OST
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| ln Vitro |
ML414 (also known NGI-1) is a novel and cell-permeable inhibitor of oligosaccharyltransferase (OST), which is a hetero-oligomeric enzyme that exists in multiple isoforms and transfers oligosaccharides to recipient proteins. ML414 was identified from a cell-based high-throughput screen and lead-compound-optimization campaign. In non-small-cell lung cancer cells, NGI-1 blocks cell-surface localization and signaling of the epidermal growth factor receptor (EGFR) glycoprotein, but selectively arrests proliferation in only those cell lines that are dependent on EGFR (or fibroblast growth factor, FGFR) for survival. In these cell lines, OST inhibition causes cell-cycle arrest accompanied by induction of p21, autofluorescence, and cell morphology changes, all hallmarks of senescence. These results identify OST inhibition as a potential therapeutic approach for treating receptor-tyrosine-kinase-dependent tumors and provides a chemical probe for reversibly regulating N-linked glycosylation in mammalian cells.
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| ln Vivo |
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| Enzyme Assay |
The HTS approach using the bioluminescent N-linked glycosylation reporter in D54-ERLucT and D54-LucT cells has been previously described. Briefly, the primary cell-based screen detects N-linked glycan site occupancy using a modified and ER translated luciferase protein with three N-linked glycosylation consensus sequons. Inhibition of glycosylation in D54-ERLucT restores and increases luciferase activity over controls whereas it does not increase activity in the non-ER translated D54-LucT cell line. The methodology for the primary (D54-ERlucT), secondary false positive (D54-LucT), and tertiary (luciferase inhibition) screens as well as toxicity assays with CellTitre Glo are deposited in Pubchem (AID 588693). Genedata Screener software with the Smartfit algorithm was used for to generate AC40 values for comparative analysis of analogs.
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| Cell Assay |
In non-small-cell lung cancer cells, NGI-1 blocks cell-surface localization and signaling of the epidermal growth factor receptor (EGFR) glycoprotein, but selectively arrests proliferation in only those cell lines that are dependent on EGFR (or fibroblast growth factor, FGFR) for survival. In these cell lines, OST inhibition causes cell-cycle arrest accompanied by induction of p21, autofluorescence, and cell morphology changes, all hallmarks of senescence. These results identify OST inhibition as a potential therapeutic approach for treating receptor-tyrosine-kinase-dependent tumors and provides a chemical probe for reversibly regulating N-linked glycosylation in mammalian cells.
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| References |
| Molecular Formula |
C17H22N4O3S2
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| Molecular Weight |
394.51
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| Exact Mass |
394.11
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| Elemental Analysis |
C, 51.76; H, 5.62; N, 14.20; O, 12.17; S, 16.25
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| CAS # |
790702-57-7
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| Appearance |
Solid powder
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| SMILES |
O=C(NC1=NC=C(C)S1)C2=CC(S(=O)(N(C)C)=O)=CC=C2N3CCCC3
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| InChi Key |
QPKGRLIYJGBKJL-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C17H22N4O3S2/c1-12-11-18-17(25-12)19-16(22)14-10-13(26(23,24)20(2)3)6-7-15(14)21-8-4-5-9-21/h6-7,10-11H,4-5,8-9H2,1-3H3,(H,18,19,22)
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| Chemical Name |
5-(dimethylsulfamoyl)-N-(5-methyl-1,3-thiazol-2-yl)-2-(pyrrolidin-1-yl)benzamide
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| Synonyms |
NGI-1; NGI1; NGI 1; ML414; ML 414; ML-414;
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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 |
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| 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 : 79~100 mg/mL ( 200.24~253.48 mM )
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.34 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (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 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL 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: ≥ 2.5 mg/mL (6.34 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 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. View More
Solubility in Formulation 3: 10% DMSO+40% PEG300+5% Tween-80+45% Saline: ≥ 2.5 mg/mL (6.34 mM); |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5348 mL | 12.6739 mL | 25.3479 mL | |
| 5 mM | 0.5070 mL | 2.5348 mL | 5.0696 mL | |
| 10 mM | 0.2535 mL | 1.2674 mL | 2.5348 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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