| Size | Price | |
|---|---|---|
| 100mg | ||
| 250mg | ||
| 500mg | ||
| Other Sizes |
| Targets |
The primary target of NSC66811 is MDM2 (murine double minute 2), a negative regulator of the tumor suppressor p53. It acts as an inhibitor of the MDM2-p53 interaction, binding to MDM2 with a Ki of 120 nM. By binding to MDM2, NSC66811 prevents MDM2 from binding to and degrading p53, leading to p53 stabilization and activation. The compound mimics three p53 residues involved in binding to MDM2.
|
|---|---|
| ln Vitro |
Because NSC 66811 (0, 5, 10, 20 μM) functionally activates p53, it causes p53, MDM2, and p21cip1/waf to accumulate in a dose-dependent manner [1].
In vitro, NSC66811 is an inhibitor of the MDM2-p53 interaction. It binds to MDM2 with a Ki of 120 nM and activates p53 in cancer cells. The compound induces p21, p53, and MDM2 accumulation in human colon cancer cells. Its activity is typically measured using binding assays that assess the displacement of a labeled p53 peptide from MDM2, or cell-based assays that measure p53 activation and downstream target gene expression. |
| ln Vivo |
In vivo, NSC66811 activates p53 in cancer cells. By disrupting the MDM2-p53 interaction, the compound stabilizes and activates p53, leading to the induction of p53 target genes and apoptosis in cancer cells. While specific in vivo efficacy data for NSC66811 are not extensively detailed in the available literature, its mechanism of action suggests that it would be effective in reducing tumor growth in p53 wild-type cancers.
|
| Enzyme Assay |
In vitro enzyme/receptor binding assays for NSC66811 involve binding studies using purified MDM2 protein or cell lysates. The compound's ability to inhibit the MDM2-p53 interaction is measured by monitoring the displacement of a labeled p53 peptide from MDM2. Ki values are determined from dose-response curves. Surface plasmon resonance (SPR) or isothermal titration calorimetry (ITC) can be employed to measure the binding affinity.
|
| Cell Assay |
Western blot analysis[1]
Cell Types: HCT-116 (p53+/+ and p53-/-) cells[1]. Tested Concentrations: 0, 5, 10, 20 μM. Incubation Duration: 48 hrs (hours). Experimental Results: Wild-type p53 dose-dependently induced the accumulation of p53, MDM2, and p21cip1/waf proteins in the HCT-116 human colon cancer cell line. There was no effect on p53, MDM2, and p21cip1/waf protein levels in the isogenic HCT-116 p53-/- cell line. In vitro cellular assays for NSC66811 are conducted in cancer cell lines with wild-type p53. Cells are treated with varying concentrations of NSC66811, and p53 activation is assessed by measuring p53 protein levels and the expression of p53 target genes such as p21 and MDM2 by western blotting or qPCR. Apoptosis is evaluated by measuring caspase activation, annexin V staining, or PARP cleavage. These assays confirm that NSC66811 engages its target in a cellular context and produces the expected activation of p53 and induction of apoptosis. |
| Animal Protocol |
In vivo animal studies for NSC66811 would typically be conducted in mouse xenograft models using cancer cell lines with wild-type p53. Animals would be administered the compound, and tumor growth inhibition would be monitored. p53 activation and apoptosis in tumors would be assessed by immunohistochemistry or western blotting. Pharmacokinetic studies would be performed to determine the compound's bioavailability, half-life, and tissue distribution.
|
| ADME/Pharmacokinetics |
Pharmacokinetic properties of NSC66811 indicate that it has a molecular weight of 340.42 and a molecular formula of C23H20N2O. The compound is soluble in ethanol (1 mg/ml), DMSO (25 mg/ml), and DMF (33 mg/ml), facilitating its use in in vitro assays and formulation for in vivo administration. The compound is cell-permeable. For storage, the powder should be kept under appropriate conditions to maintain stability.
|
| Toxicity/Toxicokinetics |
The toxicological profile of NSC66811 is primarily derived from its use as a research compound in preclinical studies. As an MDM2 inhibitor, potential on-target effects could include activation of p53 in normal tissues, leading to apoptosis and tissue damage. Comprehensive toxicology studies would be required for therapeutic development, including assessments of hematopoietic, gastrointestinal, and reproductive function.
|
| References |
|
| Additional Infomation |
NSC66811 is a novel inhibitor of the MDM2-p53 interaction. It binds to MDM2 with a Ki of 120 nM and activates p53 in cancer cells. The compound mimics three p53 residues involved in binding to MDM2. NSC66811 is cell-permeable. It is not approved for clinical use and is available from research chemical suppliers for preclinical studies.
|
| Molecular Formula |
C23H20N2O
|
|---|---|
| Molecular Weight |
340.42
|
| Exact Mass |
340.157
|
| CAS # |
6964-62-1
|
| PubChem CID |
248986
|
| Appearance |
Light brown to gray solid powder
|
| Density |
1.2±0.1 g/cm3
|
| Boiling Point |
529.5±45.0 °C at 760 mmHg
|
| Melting Point |
145 °C
|
| Flash Point |
274.0±28.7 °C
|
| Vapour Pressure |
0.0±1.4 mmHg at 25°C
|
| Index of Refraction |
1.708
|
| LogP |
4.73
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
3
|
| Rotatable Bond Count |
4
|
| Heavy Atom Count |
26
|
| Complexity |
430
|
| Defined Atom Stereocenter Count |
0
|
| InChi Key |
WEENRMPCSWFMTE-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C23H20N2O/c1-16-12-13-18-14-15-20(23(26)22(18)24-16)21(17-8-4-2-5-9-17)25-19-10-6-3-7-11-19/h2-15,21,25-26H,1H3
|
| Chemical Name |
7-[anilino(phenyl)methyl]-2-methylquinolin-8-ol
|
| Synonyms |
NSC 66811; NSC-66811; NSC66811
|
| 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) |
DMSO : ~100 mg/mL (~293.75 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (7.34 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
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 to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume 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 (7.34 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.9375 mL | 14.6877 mL | 29.3755 mL | |
| 5 mM | 0.5875 mL | 2.9375 mL | 5.8751 mL | |
| 10 mM | 0.2938 mL | 1.4688 mL | 2.9375 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
