Tenovin-6SIRT inhibitor and p53 activator CAS# 1011557-82-6 |
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Quality Control & MSDS
Number of papers citing our products
Chemical structure
3D structure
Cas No. | 1011557-82-6 | SDF | Download SDF |
PubChem ID | 24772043 | Appearance | Powder |
Formula | C25H34N4O2S | M.Wt | 454.6 |
Type of Compound | N/A | Storage | Desiccate at -20°C |
Solubility | DMSO : ≥ 31 mg/mL (68.19 mM) *"≥" means soluble, but saturation unknown. | ||
Chemical Name | 4-tert-butyl-N-[[4-[5-(dimethylamino)pentanoylamino]phenyl]carbamothioyl]benzamide | ||
SMILES | CC(C)(C)C1=CC=C(C=C1)C(=O)NC(=S)NC2=CC=C(C=C2)NC(=O)CCCCN(C)C | ||
Standard InChIKey | BVJSXSQRIUSRCO-UHFFFAOYSA-N | ||
Standard InChI | InChI=1S/C25H34N4O2S/c1-25(2,3)19-11-9-18(10-12-19)23(31)28-24(32)27-21-15-13-20(14-16-21)26-22(30)8-6-7-17-29(4)5/h9-16H,6-8,17H2,1-5H3,(H,26,30)(H2,27,28,31,32) | ||
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 | Tenovin-6 is an inhibitor of sirtuin with IC50 values of 21 µM, 10 µM and 67 µM for SIRT1, SIRT2 and SIRT3, respectively. | ||||||
Targets | SIRT1 | SIRT2 | SIRT3 | p53 | |||
IC50 | 21 µM | 10 µM | 67 µM |
Tenovin-6 Dilution Calculator
Tenovin-6 Molarity Calculator
1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
1 mM | 2.1997 mL | 10.9987 mL | 21.9974 mL | 43.9947 mL | 54.9934 mL |
5 mM | 0.4399 mL | 2.1997 mL | 4.3995 mL | 8.7989 mL | 10.9987 mL |
10 mM | 0.22 mL | 1.0999 mL | 2.1997 mL | 4.3995 mL | 5.4993 mL |
50 mM | 0.044 mL | 0.22 mL | 0.4399 mL | 0.8799 mL | 1.0999 mL |
100 mM | 0.022 mL | 0.11 mL | 0.22 mL | 0.4399 mL | 0.5499 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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Tenovin-6 is an analog of tenovin-1 with more water-soluble and it inhibits the protein deacetylase activities of SIRT1, SIRT2 and SIRT3 with IC50 value of 21 μM, 10 μM, and 67 μM, respectively [1].
It has been identified that the cytotoxic effects of tenovin-6 may occur through the dysregulation of autophagy rather than induction of apoptosis in chronic lymphocytic leukemia cells. Sir2p homologs could be targets for tenovin-6 in mammalian cells.
Tenovin-6 decreases purified human SirT1 peptide deacetylase activity in vitro with an IC50 of 21 mM and human SirT2 activity with an IC50 of 10 mM. Inhibition of SirT3 by tenovin-6 in this assay was significantly lower with an IC50 of 67 mM. And the activity of HDAC8 is poorly inhibited by tenovin-6 with an IC50 above the highest concentration of 90 mM. In xenograft models, tenovins induce apoptosis in malignant cell lines, containing those derived from lympho-reticular neoplasia and decrease human tumor growth. Anti-leukaemic properties of Sirtuin inhibitors have also been demonstrated in recent pre-clinical studies on Tenovin in chronic myeloid leukaemia and Nicotinamide in CLL15 associated with increased p53-pathway function [1, 2].
Tenovin-6 has potent antitumor activity against human gastric cancer cells via DR5 up-regulation. Interestingly, tenovin-6 induced apoptosis in the cell lines, those with wild-type TP53, mutant-type and null versions, which were accompanied by up regulation of death receptor 5. In the KatoIII cell line ( TP53-null), death receptor 5 silencing markedly attenuated tenovin-6-induced apoptosis, indicating that the pivotal mechanism behind its antitumor effects is based on activation of the death receptor signal pathway. Tenovin-6 combined with docetaxel or SN-38 exerted a slight to moderate synergistic cytotoxicity against gastric cancer cells [3].
References:
[1]. Lain S, Hollick JJ, Campbell J, et al. Discovery, in vivo activity, and mechanism of action of a small-molecule p53 activator. Cancer Cell, 2008, 13(5): 454-463.
[2]. MacCallum SF, Groves MJ, James J, et al. Dysregulation of autophagy in chronic lymphocytic leukemia with the small-molecule Sirtuin inhibitor Tenovin-6. Scientific Reports, 2013, 3: 1275.
[3]. Hirai S, Endo S, Saito R, et al. Antitumor Effects Of A Sirtuin Inhibitor, Tenovin-6, Against Gastric Cancer Cells Via Death Receptor 5 Up-Regulation. PLoS ONE, 2014, 9(7): e102831.
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Tenovin-6 impairs autophagy by inhibiting autophagic flux.[Pubmed:28182004]
Cell Death Dis. 2017 Feb 9;8(2):e2608.
Tenovin-6 has attracted significant interest because it activates p53 and inhibits sirtuins. It has anti-neoplastic effects on multiple hematopoietic malignancies and solid tumors in both in vitro and in vivo studies. Tenovin-6 was recently shown to impair the autophagy pathway in chronic lymphocytic leukemia cells and pediatric soft tissue sarcoma cells. However, whether Tenovin-6 has a general inhibitory effect on autophagy and whether there is any involvement with SIRT1 and p53, both of which are regulators of the autophagy pathway, remain unclear. In this study, we have demonstrated that Tenovin-6 increases microtubule-associated protein 1 light chain 3 (LC3-II) level in diverse cell types in a time- and dose-dependent manner. Mechanistically, the increase of LC3-II by Tenovin-6 is caused by inhibition of the classical autophagy pathway via impairing lysosomal function without affecting the fusion between autophagosomes and lysosomes. Furthermore, we have revealed that Tenovin-6 activation of p53 is cell type dependent, and Tenovin-6 inhibition of autophagy is not dependent on its regulatory functions on p53 and SIRT1. Our results have shown that Tenovin-6 is a potent autophagy inhibitor, and raised the precaution in interpreting results where Tenovin-6 is used as an inhibitor of SIRT1.
Tenovin-6-mediated inhibition of SIRT1/2 induces apoptosis in acute lymphoblastic leukemia (ALL) cells and eliminates ALL stem/progenitor cells.[Pubmed:25884180]
BMC Cancer. 2015 Apr 7;15:226.
BACKGROUND: Acute lymphoblastic leukemia (ALL) is a heterogeneous group of malignant disorders derived from B- or T-cell lymphoid progenitor cells. ALL often is refractory to or relapses after treatment; thus, novel targeted therapy for ALL is urgently needed. In the present study, we initially found that the level of SIRT1, a class III histone deacetylase, was higher in primary ALL cells from patients than in peripheral blood mononuclear cells from healthy individuals. But it is not clear whether inhibition of SIRT1 by its selective small molecule inhibitor Tenovin-6 is effective against ALL cells. METHODS: We tested the effect of Tenovin-6 on ALL cell lines (REH and NALM-6) and primary cells from 41 children with ALL and 2 adult patients with ALL. The effects of Tenovin-6 on cell viability were determined by MTS assay; colony-forming assays were determined by soft agar in ALL cell lines and methylcellulose medium in normal bone marrow cells and primary ALL blast cells; cell apoptosis and cell cycling were examined by flow cytometry; the signaling pathway was determined by Western blotting; ALL stem/progenitor cells were seperated by using MACS MicroBead kit. RESULTS: The results showed that Tenovin-6 treatment activated p53, potently inhibited the growth of pre-B ALL cells and primary ALL cells, and sensitized ALL cells to frontline chemotherapeutic agents etoposide and cytarabine. Tenovin-6 induced apoptosis in REH and NALM-6 cells and primary ALL cells and diminished expression of Mcl-1 and X-linked inhibitor of apoptosis protein (XIAP) in such cells. Furthermore, inhibition of SIRT1 by Tenovin-6 inhibited the Wnt/beta-catenin signaling pathway and eliminated ALL stem/progenitor (CD133 + CD19-) cells. CONCLUSION: Our results indicate that Tenovin-6 may be a promising targeted therapy for ALL and clinical trials are warranted to investigate its efficacy in ALL patients.
Tenovin-6 inhibits proliferation and survival of diffuse large B-cell lymphoma cells by blocking autophagy.[Pubmed:28118604]
Oncotarget. 2017 Feb 28;8(9):14912-14924.
Diffuse large B-cell lymphoma (DLBCL) is one of the most aggressive non-Hodgkin lymphomas. It is curable but one-third of cases are refractory to therapy or relapse after initial response highlighting the urgent need for developing novel therapeutic approaches. Targeting sirtuins, particularly SIRT1 by genetic approaches or using pharmaceutical inhibitor Tenovin-6, has shown promising therapeutic potential in various hematopoietic malignancies. However, it remains unknown whether these approaches are effective for DLBCL. In this study, we have found that Tenovin-6 potently inhibits the proliferation and survival of DLBCL cells. Surprisingly, specific knockdown of SIRT1/2/3 has no effect on DLBCL. Mechanistically, Tenovin-6 increases the level of microtubule-associated protein 1 light chain 3B (LC3B)-II in a SIRT1/2/3- and p53-independent manner in DLBCL cell lines. Tenovin-6-mediated increase of LC3B-II is through inhibition of classical autophagy pathway. Furthermore, inhibition of the autophagy pathway by using other inhibitors or by knocking down key genes in the pathway impairs cell proliferation and survival of DLBCL cells. These results indicate that targeting the autophagic pathway could be a novel therapeutic strategy for DLBCL and that precaution should be taken to interpret data where Tenovin-6 was used as an inhibitor of sirtuins.
Class III-specific HDAC inhibitor Tenovin-6 induces apoptosis, suppresses migration and eliminates cancer stem cells in uveal melanoma.[Pubmed:26940009]
Sci Rep. 2016 Mar 4;6:22622.
Uveal melanoma (UM) is the most common intraocular malignancy in adults. Despite improvements in surgical, radiation and chemotherapy treatments, the overall survival of UM and prognosis remain poor. In the present study, we hypothesized that Sirtuin 1 and 2 (SIRT1/2), class III histone deacetylases (HDACs), were critical in controlling the destiny of bulk tumor cells and cancer stem cells (CSCs) of UM. We testified this hypothesis in four lines of UM cells (92.1, Mel 270, Omm 1 and Omm 2.3). Our results showed that inhibition of SIRT1/2 by Tenovin-6 induced apoptosis in UM cells by activating the expression of tumor suppressor genes such as p53 and elevating reactive oxygen species (ROS). Tenovin-6 inhibited the growth of UM cells. Tenovin-6 and vinblastine was synergistic in inducing apoptosis of UM cell line 92.1 and Mel 270. Furthermore, Tenovin-6 eliminated cancer stem cells in 92.1 and Mel 270 cells. In conclusion, our findings suggest that Tenovin-6 may be a promising agent to kill UM bulk tumor cells and CSCs.