InauhzinSIRT1 inhibitor CAS# 309271-94-1 |
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Quality Control & MSDS
Number of papers citing our products
Chemical structure
3D structure
Cas No. | 309271-94-1 | SDF | Download SDF |
PubChem ID | 5494506 | Appearance | Powder |
Formula | C25H19N5OS2 | M.Wt | 469.58 |
Type of Compound | N/A | Storage | Desiccate at -20°C |
Synonyms | INZ | ||
Solubility | DMSO : 21 mg/mL (44.72 mM; Need ultrasonic and warming) | ||
Chemical Name | 1-phenothiazin-10-yl-2-(5H-[1,2,4]triazino[5,6-b]indol-3-ylsulfanyl)butan-1-one | ||
SMILES | CCC(C(=O)N1C2=CC=CC=C2SC3=CC=CC=C31)SC4=NC5=C(C6=CC=CC=C6N5)N=N4 | ||
Standard InChIKey | VHUOXERIKQWIJE-UHFFFAOYSA-N | ||
Standard InChI | 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) | ||
General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months. Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it. |
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About Packaging | 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial. 2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial. 3. Try to avoid loss or contamination during the experiment. |
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Shipping Condition | Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request. |
Description | Inauhzin is a dual SirT1/IMPDH2 inhibitor, and acts as an activator p53, used in the research of cancer.In Vitro:Inauhzin (10 µM) induces p53 levels as effectively as actinomycin D (10 nM), and mediates p53-dependent cytotoxicity through its specific functional groups in human lung carcinoma H460 cells. Inauhzin (2 µM) induces p53 level and activity as well as p53-dependent apoptosis. Inauhzin also stabilizes p53 and inhibits its ubiquitylation. Inauhzin induces acetylation of p53 in H460 cells, but not tubulin, which is affected by knockdown of SIRT1[1]. Inauhzin (0-2 µM) significantly enhances the expression level and activity of p53 in HCT116p53+/+ cells and enhances the expression level and activity of p53 in H460 cells in a dose-dependent manner. Inauhzin and Nutlin-3 demonstrate synergistic cytotoxicity in the Nutlin-3 low-sensitive cells. Inauhzin and Nutlin-3 synergistically induce p53-dependent apoptosis[2]. Inauhzin targets both SirT1 and IMP dehydrogenase 2 (IMPDH2), and acts as a potent p53 activator[3].In Vivo:Inauhzin (30 mg/kg, i.p.) effectively induces apoptosis and suppresses tumour growth of H460 xenograft harbouring p53[1]. Inauhzin (30 mg/kg, i.p.) reduces the HCT116 tumor volume by appr 70%. Inauhzin (15 mg/kg) in combination with 150 mg/kg of Nutlin-3 demonstrates a significant synergy on p53 induction, apoptosis and tumor suppression of HCT116p53+/+ xenografts[2]. References: |
Inauhzin Dilution Calculator
Inauhzin Molarity Calculator
1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
1 mM | 2.1296 mL | 10.6478 mL | 21.2956 mL | 42.5913 mL | 53.2391 mL |
5 mM | 0.4259 mL | 2.1296 mL | 4.2591 mL | 8.5183 mL | 10.6478 mL |
10 mM | 0.213 mL | 1.0648 mL | 2.1296 mL | 4.2591 mL | 5.3239 mL |
50 mM | 0.0426 mL | 0.213 mL | 0.4259 mL | 0.8518 mL | 1.0648 mL |
100 mM | 0.0213 mL | 0.1065 mL | 0.213 mL | 0.4259 mL | 0.5324 mL |
* Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations. |
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Inauhzin is a small-molecule inhibitor of SIRT1 with IC50 value of 0.7-2μM [1].
Inauhzin inhibits SIRT1 deacetylation activity and subsequently activates the substrate of SIRT1, p53, in a dose-dependent manner. It shows an induction of acetylation of p53 and Histone H3 in the K382 and K9 residues, respectively. The inhibition of SIRT1 is selective. It has no significant effect on SIRT2, SIRT3 or HDAC8 in the Fluor-de-Lys fluorimetric assay. Since it is an activator of p53, inauhzin inhibits cell growth in different p53-containing human cancer cells including H460, H1299, A549, HT29 and WI38. The IC50 values are 5.4μM, 51.9μM, 3.2μM, 33.9μM and 85.4μM, respectively. Furthermore, inauhzin induces cell apoptosis through activating p53. In the xenograft tumours derived from H460 cells, inauhzin also significantly induces p53 activity and p53-dependent apoptosis at 2μM [1].
References:
[1] Zhang Q, Zeng SX, Zhang Y, Zhang Y, Ding D, Ye Q, Meroueh SO, Lu H. A small molecule Inauhzin inhibits SIRT1 activity and suppresses tumour growth through activation of p53. EMBO Mol Med. 2012 Apr;4(4):298-312.
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The role of IMP dehydrogenase 2 in Inauhzin-induced ribosomal stress.[Pubmed:25347121]
Elife. 2014 Oct 27;3.
The 'ribosomal stress (RS)-p53 pathway' is triggered by any stressor or genetic alteration that disrupts ribosomal biogenesis, and mediated by several ribosomal proteins (RPs), such as RPL11 and RPL5, which inhibit MDM2 and activate p53. Inosine monophosphate (IMP) dehydrogenase 2 (IMPDH2) is a rate-limiting enzyme in de novo guanine nucleotide biosynthesis and crucial for maintaining cellular guanine deoxy- and ribonucleotide pools needed for DNA and RNA synthesis. It is highly expressed in many malignancies. We previously showed that inhibition of IMPDH2 leads to p53 activation by causing RS. Surprisingly, our current study reveals that Inauzhin (INZ), a novel non-genotoxic p53 activator by inhibiting SIRT1, can also inhibit cellular IMPDH2 activity, and reduce the levels of cellular GTP and GTP-binding nucleostemin that is essential for rRNA processing. Consequently, INZ induces RS and the RPL11/RPL5-MDM2 interaction, activating p53. These results support the new notion that INZ suppresses cancer cell growth by dually targeting SIRT1 and IMPDH2.
Inauhzin sensitizes p53-dependent cytotoxicity and tumor suppression of chemotherapeutic agents.[Pubmed:23633924]
Neoplasia. 2013 May;15(5):523-34.
Toxicity and chemoresistance are two major issues to hamper the success of current standard tumor chemotherapy. Combined therapy of agents with different mechanisms of action is a feasible and effective means to minimize the side effects and avoid the resistance to chemotherapeutic drugs while improving the antitumor effects. As the most essential tumor suppressor, p53 or its pathway has been an attractive target to develop a new type of molecule-targeting anticancer therapy. Recently, we identified a small molecule, Inauhzin (INZ), which can specifically activate p53 by inducing its deacetylation. In this study, we tested if combination with INZ could sensitize tumor cells to the current chemotherapeutic drugs, cisplatin (CIS) and doxorubicin (DOX). We found that compared with any single treatment, combination of lower doses of INZ and CIS or DOX significantly promoted apoptosis and cell growth inhibition in human non-small lung cancer and colon cancer cell lines in a p53-dependent fashion. This cooperative effect between INZ and CIS on tumor suppression was also confirmed in a xenograft tumor model. Therefore, this study suggests that specifically targeting the p53 pathway could enhance the sensitivity of cancer cells to chemotherapeutic agents and markedly reduce the doses of the chemotherapy, possibly decreasing its adverse side effects.
Determination of Maximum Tolerated Dose and Toxicity of Inauhzin in Mice.[Pubmed:26167454]
Toxicol Rep. 2015;2:546-554.
Reactivating the tumor suppressor p53 offers an attractive strategy for developing cancer therapy. We recently identified Inauhzin (INZ) as a novel non-genotoxic p53-activating compound. To develop INZ into a clinically applicable anticancer drug, we have initiated preclinical toxicity studies. Here, we report our study on determining the maximum tolerated dose (MTD) of INZ analog, Inauhzin-C (INZ (C)), following intraperitoneal (i.p) administration (Phase A) and its toxicity following i.p administration over a period of 5-day dosing plus 2-day recovery (Phase B) in CD-1 mice. The phase A study showed that the MTD of INZ (C) is 200 mg/kg for female and 250 mg/kg for male, respectively. The phase B study showed that the administration of INZ (C) via 5-day consecutive i.p injection is tolerated by female CD-1 mice at all dose levels tested from 50mg/kg to 120 mg/kg without significant changes in biochemical and pathological parameters in the animals. Together, these results indicate that our previously determined effective dose of INZ at 30-60 mg/kg via i.p is quite safe to mice, and imply that this compound have the features worthy for further development into a clinically applicable drug.
Inauhzin(c) inactivates c-Myc independently of p53.[Pubmed:25692307]
Cancer Biol Ther. 2015;16(3):412-9.
Oncogene MYC is deregulated in many human cancers, especially in lymphoma. Previously, we showed that Inauhzin (INZ) activates p53 and inhibits tumor growth. However, whether INZ could suppress cancer cell growth independently of p53 activity is still elusive. Here, we report that INZ(c), a second generation of INZ, suppresses c-Myc activity and thus inhibits growth of human lymphoma cells in a p53-independent manner. INZ(c) treatment decreased c-Myc expression at both mRNA and protein level, and suppressed c-Myc transcriptional activity in human Burkitt's lymphoma Raji cells with mutant p53. Also, we showed that overexpressing ectopic c-Myc rescues the inhibition of cell proliferation by INZ(c) in Raji cells, implicating c-Myc activity is targeted by INZ(c). Interestingly, the effect of INZ(c) on c-Myc expression was impaired by disrupting the targeting of c-Myc mRNA by miRNAs via knockdown of ribosomal protein (RP) L5, RPL11, or Ago2, a subunit of RISC complex, indicating that INZ(c) targets c-Myc via miRNA pathways. These results reveal a new mechanism that INZ