| Size | Price | Stock | Qty |
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| 10mg |
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| Other Sizes |
| Targets |
KVS0001 targets SMG1 kinase, a critical regulator of the nonsense-mediated decay (NMD) pathway. NMD is a quality control mechanism that degrades mRNAs containing premature termination codons. By inhibiting SMG1, KVS0001 inhibits NMD, leading to increased expression of transcripts and proteins from truncated mutations. This enhances the presentation of immunogenic peptides on cancer cells, promoting anti-tumor immunity.
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| ln Vitro |
In vitro studies demonstrate that KVS0001 is a potent inhibitor of SMG1 and nonsense-mediated decay (NMD). It elevates the expression of transcripts and proteins derived from truncated mutations. By inhibiting NMD, it increases the presentation of HLA class I-associated peptides on the surface of cancer cells. These peptides can be recognized by the immune system, promoting anti-tumor activity. Detailed IC50 values are not extensively documented.
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| ln Vivo |
In vivo activity of KVS0001 is inferred from its mechanism of action as an SMG1 inhibitor that modulates NMD. By inhibiting NMD, it may enhance immune recognition of cancer cells and have anti-tumor activity. It can be used to study NMD-related diseases including cancer and inherited diseases. Detailed in vivo efficacy data from animal models are not extensively documented in the available literature.
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| Enzyme Assay |
The in vitro enzyme/receptor binding assay for KVS0001 involves measuring its inhibitory activity against SMG1 kinase. The assay typically uses purified recombinant SMG1 enzyme incubated with the compound at varying concentrations, along with ATP and a substrate. Kinase activity is measured by quantifying phosphorylation levels using methods such as radiometric assays or fluorescence-based detection. IC50 values are determined by plotting percentage inhibition against compound concentration.
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| Cell Assay |
In vitro cell-based assays for KVS0001 are conducted using cancer cell lines to evaluate its effects on NMD and anti-tumor immunity. Cells are treated with the compound at various concentrations, and NMD inhibition is assessed by measuring the expression of NMD target transcripts using qPCR. HLA class I-associated peptide presentation is analyzed by mass spectrometry. Anti-tumor activity is evaluated using T-cell activation assays or co-culture systems.
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| Animal Protocol |
In vivo animal studies for KVS0001 would typically be conducted using immunocompetent mouse models of cancer to evaluate its effects on tumor growth and immune response. Animals would be administered the compound via appropriate routes, and tumor growth inhibition would be monitored. Immune cell infiltration and activation would be assessed by flow cytometry and immunohistochemistry. However, detailed protocols and efficacy data are not available from the search results.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of KVS0001 include a molecular formula of C27H27ClN8O3S. It is derived from SMG1i-11 (compound 11j) with improvements to address bioavailability limitations while preserving target engagement. Detailed pharmacokinetic parameters such as half-life, Cmax, and bioavailability are not extensively documented in the available literature. The compound is intended for research use only.
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| Toxicity/Toxicokinetics |
Toxicity information for KVS0001 is limited. Standard safety precautions for handling research chemicals should be followed. The compound is designated for research use only and is not for human therapeutic applications. As a modulator of NMD, it may have effects on normal cellular processes that should be evaluated in appropriate toxicity studies. No detailed toxicity data are available from the search results.
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| References | |
| Additional Infomation |
KVS0001 is a potent, rationally designed small-molecule inhibitor of SMG1 kinase, a critical regulator of the nonsense-mediated decay (NMD) pathway. It elevates expression of transcripts from truncated mutations and increases HLA class I-associated peptide presentation on cancer cells. It has anti-tumor activity and can be used to study NMD-related diseases. It is derived from SMG1i-11 with improved bioavailability.
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| Molecular Formula |
C27H27CLN8O3S
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| Molecular Weight |
579.07
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| Appearance |
Light yellow to yellow solid powder
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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 :~100 mg/mL (~172.69 mM; with sonication)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.32 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween-80 + 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 and add it to 400 μL PEG300 and mix well. Then add 50 μL Tween-80 to the above system and mix well. Then continue to add 450 μL of physiological saline to make up 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 (4.32 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 and add it to 900 μL of 20% SBE-β-CD saline solution and mix well. 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. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (4.32 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one),clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7269 mL | 8.6345 mL | 17.2691 mL | |
| 5 mM | 0.3454 mL | 1.7269 mL | 3.4538 mL | |
| 10 mM | 0.1727 mL | 0.8635 mL | 1.7269 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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