| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Targets |
NT219 targets insulin receptor substrates 1 and 2 (IRS1/2) and signal transducer and activator of transcription 3 (STAT3). By promoting IRS1/2 degradation and inhibiting STAT3 phosphorylation, it disrupts essential signaling pathways associated with various oncogenic processes. It enhances the aggregation of misfolded prion protein and affects the levels of certain molecular chaperones.
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| ln Vitro |
In vitro, NT219 is a potent dual inhibitor of IRS1/2 and STAT3. It affects IRS1/2 degradation and inhibits STAT3 phosphorylation. Its activity is characterized in cell-based assays by measuring the levels of IRS1/2 and phosphorylated STAT3 via Western blotting. It has been studied in various cancer cell lines for its antiproliferative effects.
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| ln Vivo |
In vivo, NT219 is being investigated in preclinical studies for its therapeutic potential in cancer. It has been studied in models of cancer and neurodegenerative diseases. A phase 1/2 study has been conducted to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of NT219 alone and in combination with cetuximab in adults with advanced solid tumors and head and neck cancer.
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| Enzyme Assay |
In vitro enzyme/receptor binding studies for NT219 are not typical, as its targets are signaling proteins rather than enzymes or receptors. Its activity is assessed by measuring its effects on IRS1/2 and STAT3 phosphorylation and degradation. Immunoprecipitation and Western blotting are used to evaluate its binding to and effects on these targets.
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| Cell Assay |
In vitro cellular assays for NT219 involve culturing cancer cell lines in the presence of serial dilutions of the compound. Cell viability is assessed using MTT or CellTiter-Glo assays. Apoptosis is quantified by flow cytometry with Annexin V/PI staining. The effects on IRS1/2 and STAT3 signaling are measured by Western blotting for phosphorylated STAT3 and levels of IRS1/2.
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| Animal Protocol |
In vivo animal studies for NT219 include xenograft models using human cancer cell lines. Tumor-bearing mice are treated with NT219 via injection. Endpoints include tumor volume measurement, survival analysis, and pharmacodynamic assessment of target engagement in tumor tissues by Western blotting. Standard protocols include dose-response assessment and comparison to vehicle or reference treatments.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of NT219 include a molecular weight of 412.26 and a molecular formula of C₁₆H₁₄BrNO₅S. Its IUPAC name is (E)-3-(2-bromo-3,4-dihydroxyphenyl)-N-[(3,4,5-trihydroxyphenyl)methyl]prop-2-enethioamide. It is a small molecule inhibitor designed to disrupt STAT3 signaling. Detailed pharmacokinetic parameters are available from preclinical and clinical studies.
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| Toxicity/Toxicokinetics |
Toxicological data for NT219 are derived from preclinical and early clinical studies. In animal models, it is generally well-tolerated at therapeutic doses. Phase 1/2 studies assess its safety, tolerability, and maximum tolerated dose. Common side effects may include those related to its mechanism of action on signaling pathways. Further studies are required to fully characterize its toxicity profile.
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| References |
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| Additional Infomation |
The IRS1/IRS2/STAT3 inhibitor NT219 is an inhibitor of signal transduction and transcription activator 3 (STAT3) and insulin receptor substrates 1 (IRS1) and 2 (IRS2), possessing potential antitumor activity. After administration, NT219 specifically targets and binds to IRS1/2 and STAT3. Inhibition of IRS1/2 blocks IRS1/2-mediated signaling pathways and other tumor survival pathways. Inhibition of STAT3 prevents STAT3 nuclear translocation and STAT3-mediated regulation of oncogene expression. This leads to tumor cell apoptosis and inhibits tumor cell proliferation. IRS1/2 and STAT3 are highly expressed oncogenic drivers in various human cancers, playing crucial roles in uncontrolled tumor cell proliferation and tumor drug resistance.
NT219 is a novel small molecule that acts as a dual inhibitor of IRS1/2 and STAT3. It is being investigated for its therapeutic potential in cancer and neurodegenerative diseases. A phase 1/2 clinical trial has been conducted to assess its safety and efficacy in advanced solid tumors and head and neck cancer. It is not approved for clinical use and is available for research purposes. |
| Molecular Formula |
C16H14BRNO5S
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|---|---|
| Molecular Weight |
412.255062580109
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| Exact Mass |
410.977
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| CAS # |
1198078-60-2
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| PubChem CID |
135914977
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| Appearance |
Yellow to brown solid powder
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| LogP |
2.6
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| Hydrogen Bond Donor Count |
6
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
24
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| Complexity |
454
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C(NCC1=CC(O)=C(O)C(O)=C1)(=S)/C=C/C1=CC=C(O)C(O)=C1Br
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| InChi Key |
XDDQKKXXQHUUHJ-DUXPYHPUSA-N
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| InChi Code |
InChI=1S/C16H14BrNO5S/c17-14-9(1-3-10(19)16(14)23)2-4-13(24)18-7-8-5-11(20)15(22)12(21)6-8/h1-6,19-23H,7H2,(H,18,24)/b4-2+
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| Chemical Name |
(E)-3-(2-bromo-3,4-dihydroxyphenyl)-N-[(3,4,5-trihydroxyphenyl)methyl]prop-2-enethioamide
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| Synonyms |
NT-219 NT 219 NT219
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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 : ≥ 100 mg/mL (~242.57 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4257 mL | 12.1283 mL | 24.2565 mL | |
| 5 mM | 0.4851 mL | 2.4257 mL | 4.8513 mL | |
| 10 mM | 0.2426 mL | 1.2128 mL | 2.4257 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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