Tenovin-6

• CAT Number: I000118
• CAS Number: 1011557-82-6
• Molecular Formula: C25H34N4O2S
• Molecular Weight: 454.6
• Purity: ≥95%
• Target: Sirtuin
• Solubility: DMSO 20 mg/ml; Ethanol 1 mg/ml
• Storage: Store at -20° C
• IC50: 21 uM (human SIRT1); 10 uM (human SIRT2) [1]
• InChIKey: BVJSXSQRIUSRCO-UHFFFAOYSA-N

Tenovin-6 is the water soluble analog of Tenovin-1 (HY-13423) and acts as a potent SIRT1 (IC50=21 uM) and SIRT2 (IC50= 10 uM) inhibitor as well as p53 activator.IC50 value: 21 uM (human SIRT1); 10 uM (human SIRT2) [1]Target: SIRT1; SIRT2in vitro: Tenovin-6 inhibits the growth of S. cerevisiae cultures with an IC50 of 30 μM and is more toxic to yeast than the less water-soluble tenovin-1. Tenovin-6 decreases purified human SirT1 peptide deacetylase activity in vitro with an IC50 of 21 μM and human SirT2 activity with an IC50 of 10 μM. Inhibition of SirT3 by tenovin-6 in this assay was significantly lower with an IC50 of 67 μM.Tenovin-6 does not inhibit enzymatic assays in general as the activity of a panel of 51 purified kinases was not significantly affected [1]. KIAA1967 expression is differentially downregulated in PDAC and impacts on the sensitivity of PDAC cells to the Sirt1/2 inhibitor Tenovin-6 [2]. In chronic lymphocytic leukemia (CLL) cells, Tnv-6 causes non-genotoxic cytotoxicity, without adversely affecting human clonogenic hematopoietic progenitors in vitro, or murine hematopoiesis. Mechanistically, exposure of CLL cells to Tnv-6 did not induce cellular apoptosis or p53-pathway activity [3].in vivo: Tenovin-6 was administered daily at 50 mg/kg by intraperitoneal injection. Control animals were treated with vehicle solution containing cyclodextrin 20% (w/v) (Cat. No. C0926 Sigma) and DMSO 10% (v/v). Tumor diameters were measured using calipers, and volumes were calculated using the equation V = π4/3[(d1 + d2)/4]. Median values of tumor size were calculated for each time point as well as the corresponding 95% confidence intervals [1].

Reference

[1]. Lain S, et al. Discovery, in vivo activity, and mechanism of action of a small-molecule p53 activator. Cancer Cell. 2008 May;13(5):454-63.

[2]. Wauters E, et al. Sirtuin-1 regulates acinar-to-ductal metaplasia and supports cancer cell viability in pancreatic cancer. Cancer Res. 2013 Apr 1;73(7):2357-67.

[3]. MacCallum SF, et al. Dysregulation of autophagy in chronic lymphocytic leukemia with the small-molecule Sirtuin inhibitor Tenovin-6. Sci Rep. 2013;3:1275.