| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg |
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| Targets |
The primary target is the NAADP (nicotinic acid adenine dinucleotide phosphate) receptor/channel, a novel calcium signaling pathway. Ned 19 is a non-competitive antagonist of NAADP-mediated calcium release. It blocks NAADP-induced Ca²⁺ release from acidic organelles (endolysosomes). It is membrane-permeant and can be used in intact cells.
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|---|---|
| ln Vitro |
Ned 19 (25-100 μM; 24-72 hours) inhibits the growth of cells [2]. Ned 19 (25-100 μM; 24-72 hours) dramatically lowers the quantity of cells [2]. Cell cycle study indicates that Ned 19 (25-100 μM; 24-72 hours) decreases the proportion of S phase and increases the percentage of G0/G1 phase [2]. Ned 19 causes apoptosis in a time-dependent manner (25-100 μM; 24-72 hours) [2]. Ned 19 (25-100 μM; 24-72 hours) can alter cell migratory behavior by decreasing N-cadherin expression and increasing E-cadherin expression [2].
Ned 19 inhibits NAADP-mediated Ca²⁺ signaling with an IC50 of 65 nM. It is a selective, membrane-permeant, non-competitive NAADP antagonist. It inhibits NAADP-induced calcium release in a dose-dependent manner. It shows selectivity for NAADP over other calcium signaling pathways. |
| ln Vivo |
Ned 19 (ip; 5 mg/Kg/every two days; 4 weeks) significantly inhibits the growth of tumors [2].
In vivo, Ned 19 strongly inhibits tumor growth and angiogenesis in murine models. It inhibits lung metastasis formation. It suppresses primary tumor growth and vascularization. Typical doses range from 1-10 mg/kg administered intraperitoneally. |
| Enzyme Assay |
Non-cell assays for Ned 19 include NAADP binding assays using sea urchin egg homogenates or purified NAADP receptors. The compound is incubated with a radiolabeled NAADP analog ([32P]NAADP) and the receptor preparation. Bound radioactivity is separated by filtration and quantified.
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| Cell Assay |
Cell proliferation assay[2]
Cell Types: B16 Cell Tested Concentrations: 25, 50, 100 μM Incubation Duration: 24, 48, 72 hrs (hours) Experimental Results: diminished cell proliferation. Cell viability assay [2] Cell Types: B16 Cell Tested Concentrations: 25, 50, 100 μM Incubation Duration: 24, 48, 72 hrs (hours) Experimental Results: The number of cells was Dramatically diminished. Cell cycle analysis[2] Cell Types: B16 Cell Tested Concentrations: 25, 50, 100 μM Incubation Duration: 24, 48, 72 hrs (hours) Experimental Results: The percentage of S phase diminished and the percentage of G0/G1 phase increased. Apoptosis analysis[2] Cell Types: B16 Cell Tested Concentrations: 25, 50, 100 μM Incubation Duration: 24, 48, 72 hrs (hours) Experimental Results: Induction of apoptosis in a time-dependent manner. Western Blot Analysis [2] Cell Types: B16 cells Tested Concentrations: 25, 50, 100 μM Incubation Duration: 24, 48, 72 hrs (hours) Experimental Results: N-cadherin expression diminished and E-cadherin expression increased. Cell-based assays for NAADP-mediated calcium signaling use intact cells loaded with calcium-sensitive fluorescent dyes (e.g., Fluo-4). Cells are treated with Ned 19 (0.1-10 µM) before stimulation with NAADP or NAADP precursors. Calcium flux is measured using a fluorescence plate reader or confocal microscopy. |
| Animal Protocol |
Animal/Disease Models: Adult male C57BL/6 mice [2]
Doses: 5 mg/Kg Route of Administration: intraperitoneal (ip) injection; every other day; 4 weeks Experimental Results: Tumor growth was severely impaired. In vivo, Ned 19 is tested in mouse models of cancer. A typical protocol involves intraperitoneal administration of Ned 19 (1-10 mg/kg) in mice with tumor xenografts. Tumor volume is measured, and angiogenesis is assessed by CD31 immunohistochemistry. Lung metastasis is assessed by counting metastatic nodules. |
| References |
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| Additional Infomation |
Structure in the first source
|
| Molecular Formula |
C30H31N4O3F
|
|---|---|
| Molecular Weight |
514.59054
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| Exact Mass |
514.238
|
| CAS # |
874374-25-1
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| Related CAS # |
trans-Ned 19;1354235-96-3
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| PubChem CID |
3978027
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
4.657
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| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
7
|
| Rotatable Bond Count |
6
|
| Heavy Atom Count |
38
|
| Complexity |
810
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
COC1=C(C=C(C=C1)C2C3=C(CC(N2)C(=O)O)C4=CC=CC=C4N3)CN5CCN(CC5)C6=CC=CC=C6F
|
| InChi Key |
FUHCEERDBRGPQZ-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C30H31FN4O3/c1-38-27-11-10-19(16-20(27)18-34-12-14-35(15-13-34)26-9-5-3-7-23(26)31)28-29-22(17-25(33-28)30(36)37)21-6-2-4-8-24(21)32-29/h2-11,16,25,28,32-33H,12-15,17-18H2,1H3,(H,36,37)
|
| Chemical Name |
1-[3-[[4-(2-fluorophenyl)piperazin-1-yl]methyl]-4-methoxyphenyl]-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylic acid
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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: ~125 mg/mL (~242.9 mM; with ultrasonication)
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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 | 1.9433 mL | 9.7165 mL | 19.4329 mL | |
| 5 mM | 0.3887 mL | 1.9433 mL | 3.8866 mL | |
| 10 mM | 0.1943 mL | 0.9716 mL | 1.9433 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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