| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| Other Sizes |
| Targets |
p53 (tumor suppressor protein). NSC194598 selectively inhibits the DNA-binding activity of p53, and to a lesser extent, its homologs p63 and p73. It does not affect the DNA binding of other transcription factors like E2F1, TCF1, and c-Myc.
|
|---|---|
| ln Vitro |
NSC194598 inhibits p53 sequence-specific DNA binding in vitro with an IC50 of approximately 180 nM. It shows selectivity for p53 family members without affecting other transcription factors. In human medullary thyroid carcinoma TT cells, it disrupts the transcriptional activation of the mutated RET gene, demonstrating its cellular activity.
|
| ln Vivo |
In vivo, a single dose of NSC194598 increased the survival of mice following irradiation by inhibiting p53 DNA binding. Its in vivo activity is characterized by an IC50 range of 2-40 uM for inhibiting p53. It is used to mitigate acute toxicity to normal tissues caused by radiation and chemotherapy.
|
| Enzyme Assay |
Cell-free DNA-binding assays are performed using recombinant human p53 protein and a biotinylated DNA probe containing a p53 response element. NSC194598 is incubated with the p53 protein, followed by the addition of the DNA probe. The p53-DNA complex is captured on a streptavidin-coated plate and detected by an anti-p53 antibody in an ELISA format.
|
| Cell Assay |
Human medullary thyroid carcinoma TT cells (which harbor a mutant RET gene) are treated with NSC194598. The effect on transcriptional activation is measured by quantifying the expression of downstream genes activated by the mutated RET. Alternatively, cells can be treated with radiation and the effect on p53 target gene induction is measured by qRT-PCR.
|
| Animal Protocol |
Male C57BL/6 mice are exposed to a lethal dose of whole-body gamma-irradiation. NSC194598 is administered via intraperitoneal injection 30-60 minutes before or after irradiation. Animal survival is monitored daily for up to 30 days. For biomarker analysis, tissues are collected at various time points post-irradiation to measure p53 target gene expression by qRT-PCR and protein levels by Western blot.
|
| ADME/Pharmacokinetics |
Pharmacokinetic data for NSC194598 are limited. The compound has a molecular weight of 317.38. It is typically dissolved in DMSO for in vitro use. For in vivo studies, it can be formulated in a mixture of DMSO, PEG300, Tween 80, and saline. Its in vivo half-life and oral bioavailability have not been fully characterized in the literature.
|
| Toxicity/Toxicokinetics |
No specific toxicity data are reported for NSC194598 as a standalone drug. However, its primary use is to protect normal tissues from the toxic effects of radiation and chemotherapy. By inhibiting p53, it reduces apoptosis in normal cells, thereby reducing acute toxicities like gastrointestinal syndrome and myelosuppression.
|
| References |
|
| Additional Infomation |
Other information: NSC194598 is a research tool validated in mouse models to demonstrate that p53 DNA binding can be targeted to reduce treatment-related toxicity. Its ability to inhibit mutant RET transcription in TT cells suggests a potential role in medullary thyroid cancer research. It is not a clinically approved drug and is for research use only.
|
| Molecular Formula |
C20H19N3O
|
|---|---|
| Molecular Weight |
317.38
|
| Exact Mass |
317.153
|
| CAS # |
5358-76-9
|
| PubChem CID |
3246550
|
| Appearance |
Light yellow to yellow solid powder
|
| Density |
1.34g/cm3
|
| Boiling Point |
535.2ºC at 760mmHg
|
| Flash Point |
277.5ºC
|
| LogP |
4.234
|
| Hydrogen Bond Donor Count |
0
|
| Hydrogen Bond Acceptor Count |
3
|
| Rotatable Bond Count |
2
|
| Heavy Atom Count |
24
|
| Complexity |
452
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
C1CCN(CC1)CC2=NC3=CC=CC4=C3C(=[N+]2[O-])C5=CC=CC=C45
|
| InChi Key |
XLBPYZGSLNDDSB-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C20H19N3O/c24-23-18(13-22-11-4-1-5-12-22)21-17-10-6-9-15-14-7-2-3-8-16(14)20(23)19(15)17/h2-3,6-10H,1,4-5,11-13H2
|
| Chemical Name |
2-oxido-3-(piperidin-1-ylmethyl)-4-aza-2-azoniatetracyclo[7.6.1.05,16.010,15]hexadeca-1,3,5,7,9(16),10,12,14-octaene
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| 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
|
|---|---|
| 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 | 3.1508 mL | 15.7540 mL | 31.5080 mL | |
| 5 mM | 0.6302 mL | 3.1508 mL | 6.3016 mL | |
| 10 mM | 0.3151 mL | 1.5754 mL | 3.1508 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
