| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
hSMG-1 <0.05 nM (IC50) mTOR 45 nM (IC50) PI3Kα 61 nM (IC50) PI3Kγ 92 nM (IC50) CDK1 32 μM (IC50) CDK2 7.1 μM (IC50)
hSMG-1 inhibitor 11e targets hSMG-1 (human suppressor of morphogenesis in genitalia-1), a serine/threonine protein kinase that is a key component of the nonsense-mediated mRNA decay (NMD) pathway. hSMG-1 phosphorylates the NMD factor UPF1, which is essential for the recognition and degradation of mRNAs containing premature termination codons. By potently inhibiting hSMG-1 with an IC50 of <0.05 nM and showing >900-fold selectivity over related kinases, this compound is a valuable tool for studying RNA surveillance and gene regulation. |
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| ln Vitro |
hSMG-1 kinase is involved in both the cellular genotoxic stress response and nonsense-mediated RNA decay (NMD), two extremely conserved RNA surveillance pathways. Dysregulation of cellular responses to stress can result in chemotherapy resistance and tumor progression, making hSMG-1 a viable target for cancer treatment [1].
In vitro, hSMG-1 inhibitor 11e demonstrates potent inhibition of hSMG-1 with an IC50 of <0.05 nM. It shows >900-fold selectivity over mTOR (IC50 of 45 nM), PI3Kα/γ (IC50s of 61 nM and 92 nM), and CDK1/CDK2 (IC50s of 32 µM and 7.1 µM). By inhibiting hSMG-1 activity, the compound interferes with NMD, leading to the stabilization of mRNAs containing premature stop codons. These in vitro characteristics support its use in studying NMD and gene regulation. |
| ln Vivo |
In vivo data for hSMG-1 inhibitor 11e is limited in publicly available sources. As a potent and selective hSMG-1 inhibitor that interferes with NMD, the compound has potential applications in animal models of diseases caused by nonsense mutations, such as certain genetic disorders and cancers. By stabilizing mRNAs containing premature stop codons, it could restore the expression of functional proteins. However, specific published in vivo efficacy studies are not widely reported. hSMG-1 inhibitor 11e is primarily used as a research tool.
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| Enzyme Assay |
The in vitro hSMG-1 inhibition assay for hSMG-1 inhibitor 11e uses recombinant hSMG-1 kinase and a peptide substrate. Kinase activity is measured using radioactive or luminescent detection methods, and IC50 values are calculated from dose-response curves. Selectivity profiling against mTOR, PI3Kα/γ, CDK1, and CDK2 is performed using similar kinase assay formats. NMD inhibition is confirmed by measuring the stabilization of NMD reporter mRNAs or endogenous NMD targets.
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| Cell Assay |
Cellular assays for hSMG-1 inhibitor 11e are conducted in cell lines with functional NMD. Cells are treated with varying concentrations of the compound. NMD activity is assessed by measuring the levels of NMD target mRNAs using qPCR or reporter assays. hSMG-1 phosphorylation of UPF1 is measured by Western blotting using phospho-specific antibodies. Cell viability and proliferation are measured using standard assays. The compound's effects on gene expression are analyzed by RNA sequencing.
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| Animal Protocol |
In vivo studies for hSMG-1 inhibitor 11e would typically involve animal models of diseases caused by nonsense mutations, such as mouse models of genetic disorders or cancer. The compound would be administered via intraperitoneal or oral routes at doses determined by pharmacokinetic studies. Efficacy would be assessed by measuring the restoration of functional protein expression and disease phenotype improvement. However, specific published in vivo protocols for hSMG-1 inhibitor 11e are not available in the current literature.
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| ADME/Pharmacokinetics |
Pharmacokinetic data for hSMG-1 inhibitor 11e is not extensively reported in publicly available sources. The compound has a molecular weight of 517.60 g/mol and a molecular formula of C26H27N7O3S. As a small molecule kinase inhibitor, it is expected to have moderate bioavailability. Storage conditions: powder at -20°C for 3 years or 4°C for 2 years; in solvent at -80°C for 6 months or -20°C for 1 month. Detailed PK parameters such as half-life are not available in the current literature.
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| Toxicity/Toxicokinetics |
Toxicity data for hSMG-1 inhibitor 11e is limited in publicly available sources. As with all research compounds, hSMG-1 inhibitor 11e is intended for research use only and not for human therapeutic applications. The compound's high selectivity for hSMG-1 over other kinases suggests a favorable off-target profile. Standard in vitro cytotoxicity assays and in vivo tolerability studies would be required for a complete toxicity assessment.
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| References | |
| Additional Infomation |
hSMG-1 inhibitor 11e is a potent and selective hSMG-1 kinase inhibitor with an IC50 of <0.05 nM. It shows >900-fold selectivity over mTOR, PI3Kα/γ, and CDK1/CDK2. By inhibiting hSMG-1, the compound interferes with NMD, leading to stabilization of mRNAs containing premature stop codons. It has a molecular formula of C26H27N7O3S and a molecular weight of 517.60 g/mol. hSMG-1 inhibitor 11e is a valuable research tool for studying RNA surveillance and gene regulation.
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| Molecular Formula |
C26H27N7O3S
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|---|---|
| Molecular Weight |
517.60268330574
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| Exact Mass |
517.189
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| CAS # |
1402452-10-1
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| PubChem CID |
71458574
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| Appearance |
White to light yellow solid powder
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| LogP |
2.9
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
37
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| Complexity |
844
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| Defined Atom Stereocenter Count |
0
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| SMILES |
S(C1C=C(C=CC=1C)NC1N=CC=C(C2C=CN=C(C=2)C2C=CC(=CC=2)NC(NC)=O)N=1)(N(C)C)(=O)=O
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| InChi Key |
FOFHDVOENOAIGR-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C26H27N7O3S/c1-17-5-8-21(16-24(17)37(35,36)33(3)4)30-25-29-14-12-22(32-25)19-11-13-28-23(15-19)18-6-9-20(10-7-18)31-26(34)27-2/h5-16H,1-4H3,(H2,27,31,34)(H,29,30,32)
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| Chemical Name |
1-[4-[4-[2-[3-(dimethylsulfamoyl)-4-methylanilino]pyrimidin-4-yl]pyridin-2-yl]phenyl]-3-methylurea
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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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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 : 50 mg/mL (96.60 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 5 mg/mL (9.66 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 50.0 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: 5 mg/mL (9.66 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9320 mL | 9.6600 mL | 19.3199 mL | |
| 5 mM | 0.3864 mL | 1.9320 mL | 3.8640 mL | |
| 10 mM | 0.1932 mL | 0.9660 mL | 1.9320 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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