| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg | |||
| 500mg | |||
| Other Sizes |
Purity: ≥98%
| Targets |
SIRT1; MDM-2/p53; IMPDH2
Inauhzin targets SIRT1 (sirtuin 1), a NAD+-dependent deacetylase that regulates the activity of various transcription factors, including p53. By inhibiting SIRT1, Inauhzin prevents the deacetylation of p53, leading to p53 activation and p53-dependent apoptosis. It also acts as an IMPDH2 inhibitor. Its dual inhibition contributes to its anticancer activity. |
|---|---|
| ln Vitro |
Inauhzin (10 µM) induces p53 levels as effectively as actinomycin D (10 nM) and mediates p53-dependent cytotoxicity through its particular functional groups in human lung carcinoma H460 cells. At 2 µM, inauhzin induces p53-dependent apoptosis as well as p53 level and activity. Moreover, inauhzin prevents p53 from being ubiquitylated and stabilizes it. In H460 cells, inauhzin acetylates p53, but not tubulin, which is impacted by SIRT1 knockdown[1]. The study found that inauhzin (0–2 µM) significantly increases the expression level and activity of p53 in HCT116p53+/+ cells and dose-dependently increases these same parameters in H460 cells. In the Nutlin-3 low-sensitive cells, inauhzin and Nutlin-3 exhibit synergistic cytotoxicity. Apoptosis dependent on p53 is synergistically induced by Inauhzin and Nutlin-3[2]. Inauhzin functions as a strong p53 activator and targets both SirT1 and IMP dehydrogenase 2 (IMPDH2)[3].
Inauhzin is a cell-permeable inhibitor of SIRT1 with an IC50 of 0.7 to 2 μM. It effectively reactivates p53 by inhibiting SIRT1 activity and promotes p53-dependent apoptosis of human cancer cells without causing apparently genotoxic stress. It inhibits cell proliferation. Its activity has been confirmed in various in vitro and in vivo studies. |
| ln Vivo |
Inauhzin (30 mg/kg, i.p.) efficiently induces apoptosis and inhibits the growth of tumors in H460 xenografts that harbor p53[1]. About 70% less HCT116 tumor volume is present when inauhzin (30 mg/kg, i.p.) is administered. When administered in conjunction with 150 mg/kg of Nutlin-3, inauhzin (15 mg/kg) significantly enhances p53 induction, apoptosis, and tumor suppression in HCT116p53+/+ xenografts[2].
Inauhzin promotes p53-dependent apoptosis of human cancer cells without causing apparently genotoxic stress. It inhibits cell proliferation. It has been used in research of cancer. Its ability to reactivate p53 through SIRT1 inhibition makes it a potential therapeutic agent for cancer. |
| Enzyme Assay |
The primary in vitro assays for Inauhzin include SIRT1 deacetylase activity assays. The enzyme is incubated with a fluorogenic acetylated peptide substrate, and the deacetylation is measured in the presence of the compound. The IC50 for SIRT1 inhibition is determined. p53 activation is assessed by measuring p53 acetylation and the expression of p53 target genes, such as p21 and PUMA, by Western blot or qPCR.
|
| Cell Assay |
Cell growth is evaluated using the cell counting kit. In 96-well culture plates, cell suspensions are seeded at 5000 cells per well and incubated at 37°C for the entire night. After adding compounds to the plates, they are incubated for 72 hours at 37°C. WST-8 is added to each well at a final concentration of 10% to determine the amount of cell growth inhibition, and the absorbance of the samples is measured using a Microplate Reader at 450 nm[1].
In vitro cellular experiments for Inauhzin involve treating cancer cells with the compound and measuring its effects on SIRT1 activity, p53 acetylation, and apoptosis. The inhibition of SIRT1 is assessed by measuring the acetylation of p53 or other SIRT1 substrates. p53-dependent apoptosis is assessed by measuring caspase activation, annexin V staining, or cell viability. |
| Animal Protocol |
Female SCID mice that are five weeks old are kept in a BSL2 environment. Mice receive a subcutaneous inoculation of either 3×106 HCT116 or 5×106 H460 cells. Every other day, the growth of tumors is observed using two-dimensional electronic digital calipers. Tumor volume (mm3) = (length × width2)/2 is the formula used to calculate tumor volume. After 7 to 9 days, when the average tumor volume is about 100 mm3, animals are given an intraperitoneal injection of either inauhzin or a vehicle (5% DMSO). On the final day of treatment, the amount of tumor growth inhibition is determined. Tumors are taken and broken up in RIPA buffer together with a combination of protease inhibitors in order to identify p53 activation in vivo. Analysis of tumour lysates is done by IB. BrdU labeling is used to measure the proliferation of cells in tumors, and then immunostaining is applied. Mice are given an intraperitoneal injection of 200 mg/kg body weight of BrdU two hours prior to their sacrifice. TUNEL staining with the Fluorescein In situ cell death detection kit is used to investigate apoptosis[1].
In vivo animal experiments for Inauhzin have been conducted in tumor xenograft models to assess its anti-tumor efficacy. The compound is administered systemically, and its effects on tumor growth and p53 activation are assessed. Its pharmacokinetic properties and safety profile are also evaluated. |
| ADME/Pharmacokinetics |
Inauhzin has a molecular weight of 469.58 and a molecular formula of C25H19N5OS2. It is a cell-permeable SIRT1 inhibitor. The compound has a CAS number of 309271-94-1. It has a purity of >98%. It is a dual SirT1/IMPDH2 inhibitor used in cancer research.
|
| Toxicity/Toxicokinetics |
Inauhzin is a research compound that is not intended for human use. Its toxicological profile is not extensively characterized in the available literature. It is reported to promote p53-dependent apoptosis without causing genotoxic stress. As with all research chemicals, standard safety precautions should be followed when handling.
|
| References |
|
| Additional Infomation |
Inauhzin (INZ) is a cell-permeable inhibitor of SIRT1 and a dual SirT1/IMPDH2 inhibitor. It effectively reactivates p53 by inhibiting SIRT1 activity, promoting p53-dependent apoptosis of human cancer cells without causing apparently genotoxic stress. Inauhzin inhibits cell proliferation and is used in cancer research.
|
| Molecular Formula |
C25H19N5OS2
|
|---|---|
| Molecular Weight |
469.581261873245
|
| Exact Mass |
469.103
|
| Elemental Analysis |
C, 63.94; H, 4.08; N, 14.91; O, 3.41; S, 13.66
|
| CAS # |
309271-94-1
|
| Related CAS # |
309271-94-1
|
| PubChem CID |
5494506
|
| Appearance |
White solid powder
|
| Density |
1.5±0.1 g/cm3
|
| Boiling Point |
773.6±70.0 °C at 760 mmHg
|
| Flash Point |
421.7±35.7 °C
|
| Vapour Pressure |
0.0±2.7 mmHg at 25°C
|
| Index of Refraction |
1.816
|
| LogP |
5.18
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
6
|
| Rotatable Bond Count |
4
|
| Heavy Atom Count |
33
|
| Complexity |
690
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
CCC(SC1=NN=C2C(NC3=C2C=CC=C3)=N1)C(N4C5=C(C=CC=C5)SC6=CC=CC=C46)=O
|
| InChi Key |
VHUOXERIKQWIJE-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C25H19N5OS2/c1-2-19(33-25-27-23-22(28-29-25)15-9-3-4-10-16(15)26-23)24(31)30-17-11-5-7-13-20(17)32-21-14-8-6-12-18(21)30/h3-14,19H,2H2,1H3,(H,26,27,29)
|
| Chemical Name |
1-phenothiazin-10-yl-2-(5H-[1,2,4]triazino[5,6-b]indol-3-ylsulfanyl)butan-1-one
|
| Synonyms |
Inauhzin
|
| 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: 94~100 mg/mL (200.2~213 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.32 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 45% Saline (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 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1296 mL | 10.6478 mL | 21.2956 mL | |
| 5 mM | 0.4259 mL | 2.1296 mL | 4.2591 mL | |
| 10 mM | 0.2130 mL | 1.0648 mL | 2.1296 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
COA
