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| 500mg |
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| Targets |
The primary target of (E/Z)-NSAH is ribonucleotide reductase (RR), the enzyme that catalyzes the conversion of ribonucleoside diphosphates to deoxyribonucleoside diphosphates, which are essential for DNA synthesis and repair. Ribonucleotide reductase is a validated target for anticancer and antiviral therapies. (E/Z)-NSAH functions as a non-nucleoside inhibitor that binds reversibly and competitively to the enzyme. The compound's mixed E/Z geometric isomer form may influence its binding affinity and selectivity for the RR enzyme.
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| ln Vitro |
In cell-free enzymatic assays, (E/Z)-NSAH inhibits ribonucleotide reductase with an IC50 of 32 μM. This activity represents the compound's direct inhibitory effect on the purified enzyme in the absence of cellular uptake or metabolism barriers. The cell-free IC50 value is significantly higher than the cell-based IC50, indicating that the compound may be more potent in the cellular environment. The compound acts as a competitive inhibitor, suggesting it competes with the natural substrate for binding to the enzyme's active site.
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| ln Vivo |
In cell-based assays, (E/Z)-NSAH inhibits ribonucleotide reductase activity with an IC50 of approximately 250 nM, which is substantially more potent than its cell-free IC50 of 32 μM. This discrepancy suggests that the compound may be actively accumulated in cells or that cellular metabolism converts it to a more active form. By inhibiting ribonucleotide reductase, (E/Z)-NSAH reduces the cellular pool of deoxyribonucleotides, thereby inhibiting DNA synthesis and cellular proliferation. The compound is a valuable tool for studying nucleotide metabolism and cell proliferation.
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| Enzyme Assay |
The cell-free assay for ribonucleotide reductase inhibition typically involves measuring the conversion of radiolabeled CDP to dCDP in the presence of the inhibitor. The reaction mixture contains purified RR enzyme, substrate (CDP or ADP), reducing agents (dithiothreitol), and the inhibitor at various concentrations. The reaction is incubated at 37°C for 30-60 minutes, and the product is separated from substrate by ion-exchange chromatography or precipitation. The IC50 value is determined by plotting percent inhibition versus inhibitor concentration and fitting the data to a sigmoidal dose-response curve.
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| Cell Assay |
The cell-based assay for (E/Z)-NSAH involves culturing mammalian cells in appropriate media and treating them with the compound at concentrations ranging from 10 nM to 100 μM. Cells are typically incubated for 24-72 hours, and cell viability is assessed using MTT, CCK-8, or ATP-based luminescence assays. The effect on DNA synthesis can be measured by [3H]-thymidine incorporation or BrdU labeling. The IC50 of approximately 250 nM is determined from dose-response curves. The compound's effects on cell cycle progression can be analyzed by flow cytometry.
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| Animal Protocol |
There is no established animal experimental protocol for (E/Z)-NSAH specifically. As a ribonucleotide reductase inhibitor, the compound could potentially be evaluated in animal models of cancer. Typical protocols for RR inhibitors involve administration to tumor-bearing mice via intraperitoneal or oral routes at doses ranging from 10-100 mg/kg, administered daily or every other day for 2-4 weeks. Tumor volumes are measured, and tissues are collected for analysis of RR activity, deoxynucleotide pools, and biomarkers of DNA damage and apoptosis.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of (E/Z)-NSAH have not been extensively reported in the literature. As a small molecule with molecular weight of 306.32 g/mol and a hydrazone structure, the compound is expected to have moderate oral bioavailability and reasonable tissue penetration. The E/Z isomer mixture may exhibit different pharmacokinetic profiles. The compound's solubility and stability characteristics would influence its absorption and distribution. Further pharmacokinetic studies would be required to determine plasma half-life, clearance, volume of distribution, and metabolic pathways.
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| Toxicity/Toxicokinetics |
Toxicity data for (E/Z)-NSAH are not well documented in the available literature. As an inhibitor of ribonucleotide reductase, the compound would be expected to have antiproliferative effects on rapidly dividing cells, which could translate to toxicity in bone marrow, gastrointestinal epithelium, and other highly proliferative tissues. Standard toxicity studies in rodents would be required to determine the maximum tolerated dose, target organ toxicity, and safety profile. The compound is intended for research use only and is not approved for human therapeutic applications.
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| References | |
| Additional Infomation |
The structure given in the first document
(E/Z)-NSAH is a research compound used to study ribonucleotide reductase inhibition and nucleotide metabolism. It is an isoform of NSAH and serves as a valuable tool for investigating the role of RR in cellular proliferation and DNA synthesis. The compound's significantly different IC50 values between cell-free (32 μM) and cell-based (~250 nM) assays highlight the importance of cellular context in drug activity. This product is intended for research use only and is not for human therapeutic applications. |
| Molecular Formula |
C18H14N2O3
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|---|---|
| Molecular Weight |
306.32
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| Exact Mass |
306.1
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| Elemental Analysis |
C, 70.58; H, 4.61; N, 9.15; O, 15.67
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| CAS # |
54009-54-0
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| Related CAS # |
54009-54-0
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| PubChem CID |
135458654
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| Appearance |
Typically exists as solid at room temperature
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| Density |
1.4g/cm3
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| Boiling Point |
526.2ºC at 760 mmHg
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| Flash Point |
272.1ºC
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| Index of Refraction |
1.734
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| LogP |
3.229
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
23
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| Complexity |
440
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1=CC=C2C(=C1)C=CC(=C2C=NNC(=O)C3=CC=CC=C3O)O
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| InChi Key |
ZZSJOLDICPVVAV-YBFXNURJSA-N
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| InChi Code |
InChI=1S/C18H14N2O3/c21-16-8-4-3-7-14(16)18(23)20-19-11-15-13-6-2-1-5-12(13)9-10-17(15)22/h1-11,21-22H,(H,20,23)/b19-11+
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| Chemical Name |
2-hydroxy-N-[(E)-(2-hydroxynaphthalen-1-yl)methylideneamino]benzamide
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| Synonyms |
SD49-7; J3.555.273A; 2-hydroxy-1-naphthalaldehyde salicyloylhydrazone; ZINC259636; AKOS001601386
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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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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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 | 3.2646 mL | 16.3228 mL | 32.6456 mL | |
| 5 mM | 0.6529 mL | 3.2646 mL | 6.5291 mL | |
| 10 mM | 0.3265 mL | 1.6323 mL | 3.2646 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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