Tenovin-6 HCl
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MedKoo CAT#: 406433

CAS#: 1011301-29-3 (HCl)

Description: Tenovin-6, also known as Tnv-6, is a bioactive small molecule SIRT2 inhibitor with anti-neoplastic activity. Inhibition of the Sirtuin class of protein deacetylases with activation of p53 function is associated with the pro-apoptotic effects of Tnv-6 in many tumors. 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. Transcriptomic profiling identified a gene program influenced by Tnv-6 that included autophagy-lysosomal pathway genes.


Chemical Structure

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Tenovin-6 HCl
CAS# 1011301-29-3 (HCl)

Theoretical Analysis

MedKoo Cat#: 406433
Name: Tenovin-6 HCl
CAS#: 1011301-29-3 (HCl)
Chemical Formula: C25H35ClN4O2S
Exact Mass:
Molecular Weight: 491.09
Elemental Analysis: C, 61.14; H, 7.18; Cl, 7.22; N, 11.41; O, 6.52; S, 6.53

Price and Availability

Size Price Availability Quantity
10.0mg USD 90.0 Ready to ship
25.0mg USD 150.0 Ready to ship
50.0mg USD 250.0 Ready to ship
100.0mg USD 450.0 Ready to ship
200.0mg USD 650.0 Ready to ship
500.0mg USD 1250.0 Ready to ship
1.0g USD 2250.0 2 Weeks
2.0g USD 3850.0 2 Weeks
5.0g USD 5950.0 2 Weeks
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Related CAS #: 1011301-29-3 (HCl)   1011557-82-6 (free base)    

Synonym: Tenovin6; Tenovin 6; Tenovin-6; Tnv-6; Tenovin-6 HCl

IUPAC/Chemical Name: 4-(tert-butyl)-N-((4-(5-(dimethylamino)pentanamido)phenyl)carbamothioyl)benzamide hydrochloride

InChi Key: UBNCTIDXQDCEPI-UHFFFAOYSA-N

InChi Code: InChI=1S/C25H34N4O2S.ClH/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);1H

SMILES Code: O=C(NC(NC1=CC=C(NC(CCCCN(C)C)=O)C=C1)=S)C2=CC=C(C(C)(C)C)C=C2.[H]Cl

Appearance: Yellow solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

Biological target: Tenovin-6 Hydrochloride is an activator of p53 transcriptional activity and inhibits the protein deacetylase activities of purified human SIRT1, SIRT2, and SIRT3 with IC50s of 21 μM, 10 μM, and 67 μM, respectively.
In vitro activity: To further confirm the inhibitory effect of tenovin-6 on autophagic flux, this study challenged the cells with Torin 1, a potent inhibitor of catalytic mechanistic target of rapamycin, to induce autophagy and examined SQSTM1/p62 level by western blotting and immunofluorescence assay. Torin 1 treatment induced LC3B-II (Figure 3a). Tenovin-6 treatment increased the number and intensity of autophagic vesicles with or without the presence of Torin 1. Taken together, these results indicated that tenovin-6 inhibited the autophagic flux induced by Torin 1. Reference: Cell Death Dis. 2017 Feb; 8(2): e2608. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5386474/
In vivo activity: Of the 7 mice in control group, 2 (28.6%), 4 (57.1%) and 6 (85.7%) developed PEL (primary effusion lymphoma) at week 3, 4 and 6 post-inoculation, respectively, while of the 8 mice treated with Tenovin-6, 0 (0%), 2 (25%) and 2 (25%) developed PEL, respectively, at the same time points (Figure 6A). Tenovin-6 significantly extended the survival of mice compared to those treated with vehicle control (undefined vs 42 days, P <0.01) (Figure 6B). All mice in control group developed ascites while only 3 of 8 mice (37.5%) in the Tenovin-6 group developed ascites. The Tenovin-6 group also had significantly less ascites than the control group (P< 0.01) (Figure 6C). Reference: J Pathol. 2017 Jul; 242(3): 309–321. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5503455/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 49.0 99.78

Preparing Stock Solutions

The following data is based on the product molecular weight 491.09 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Ke X, Qin Q, Deng T, Liao Y, Gao SJ. Heterogeneous Responses of Gastric Cancer Cell Lines to Tenovin-6 and Synergistic Effect with Chloroquine. Cancers (Basel). 2020 Feb 5;12(2):365. doi: 10.3390/cancers12020365. PMID: 32033497; PMCID: PMC7072542. 2. Yuan H, Tan B, Gao SJ. Tenovin-6 impairs autophagy by inhibiting autophagic flux. Cell Death Dis. 2017 Feb 9;8(2):e2608. doi: 10.1038/cddis.2017.25. Erratum in: Cell Death Dis. 2018 Jul 16;9(8):790. PMID: 28182004; PMCID: PMC5386474. 3. Sun J, Li G, Liu Y, Ma M, Song K, Li H, Zhu D, Tang X, Kong J, Yuan X. Targeting histone deacetylase SIRT1 selectively eradicates EGFR TKI-resistant cancer stem cells via regulation of mitochondrial oxidative phosphorylation in lung adenocarcinoma. Neoplasia. 2020 Jan;22(1):33-46. doi: 10.1016/j.neo.2019.10.006. Epub 2019 Nov 22. PMID: 31765940; PMCID: PMC6881627. 4. He M, Tan B, Vasan K, Yuan H, Cheng F, Ramos da Silva S, Lu C, Gao SJ. SIRT1 and AMPK pathways are essential for the proliferation and survival of primary effusion lymphoma cells. J Pathol. 2017 Jul;242(3):309-321. doi: 10.1002/path.4905. Epub 2017 May 13. PMID: 28393364; PMCID: PMC5503455.
In vitro protocol: 1. Ke X, Qin Q, Deng T, Liao Y, Gao SJ. Heterogeneous Responses of Gastric Cancer Cell Lines to Tenovin-6 and Synergistic Effect with Chloroquine. Cancers (Basel). 2020 Feb 5;12(2):365. doi: 10.3390/cancers12020365. PMID: 32033497; PMCID: PMC7072542. 2. Yuan H, Tan B, Gao SJ. Tenovin-6 impairs autophagy by inhibiting autophagic flux. Cell Death Dis. 2017 Feb 9;8(2):e2608. doi: 10.1038/cddis.2017.25. Erratum in: Cell Death Dis. 2018 Jul 16;9(8):790. PMID: 28182004; PMCID: PMC5386474.
In vivo protocol: 1. Sun J, Li G, Liu Y, Ma M, Song K, Li H, Zhu D, Tang X, Kong J, Yuan X. Targeting histone deacetylase SIRT1 selectively eradicates EGFR TKI-resistant cancer stem cells via regulation of mitochondrial oxidative phosphorylation in lung adenocarcinoma. Neoplasia. 2020 Jan;22(1):33-46. doi: 10.1016/j.neo.2019.10.006. Epub 2019 Nov 22. PMID: 31765940; PMCID: PMC6881627. 2. He M, Tan B, Vasan K, Yuan H, Cheng F, Ramos da Silva S, Lu C, Gao SJ. SIRT1 and AMPK pathways are essential for the proliferation and survival of primary effusion lymphoma cells. J Pathol. 2017 Jul;242(3):309-321. doi: 10.1002/path.4905. Epub 2017 May 13. PMID: 28393364; PMCID: PMC5503455.

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1: Groves MJ, Johnson CE, James J, Prescott AR, Cunningham J, Haydock S, Pepper C, Fegan C, Pirrie L, Westwood NJ, Coates PJ, Ganley IG, Tauro S. p53 and cell cycle independent dysregulation of autophagy in chronic lymphocytic leukaemia. Br J Cancer. 2013 Oct 29;109(9):2434-44. doi: 10.1038/bjc.2013.601. Epub 2013 Oct 3. PubMed PMID: 24091621; PubMed Central PMCID: PMC3817336.

2: Sunami Y, Araki M, Hironaka Y, Morishita S, Kobayashi M, Liew EL, Edahiro Y, Tsutsui M, Ohsaka A, Komatsu N. Inhibition of the NAD-dependent protein deacetylase SIRT2 induces granulocytic differentiation in human leukemia cells. PLoS One. 2013;8(2):e57633. doi: 10.1371/journal.pone.0057633. Epub 2013 Feb 27. PubMed PMID: 23460888; PubMed Central PMCID: PMC3584049.

3: MacCallum SF, Groves MJ, James J, Murray K, Appleyard V, Prescott AR, Drbal AA, Nicolaou A, Cunningham J, Haydock S, Ganley IG, Westwood NJ, Coates PJ, Lain S, Tauro S. Dysregulation of autophagy in chronic lymphocytic leukemia with the small-molecule Sirtuin inhibitor Tenovin-6. Sci Rep. 2013;3:1275. doi: 10.1038/srep01275. PubMed PMID: 23429453; PubMed Central PMCID: PMC3572444.

4: Wauters E, Sanchez-Arévalo Lobo VJ, Pinho AV, Mawson A, Herranz D, Wu J, Cowley MJ, Colvin EK, Njicop EN, Sutherland RL, Liu T, Serrano M, Bouwens L, Real FX, Biankin AV, Rooman I. Sirtuin-1 regulates acinar-to-ductal metaplasia and supports cancer cell viability in pancreatic cancer. Cancer Res. 2013 Apr 1;73(7):2357-67. doi: 10.1158/0008-5472.CAN-12-3359. Epub 2013 Jan 31. PubMed PMID: 23370328.

5: McCarthy AR, Sachweh MC, Higgins M, Campbell J, Drummond CJ, van Leeuwen IM, Pirrie L, Ladds MJ, Westwood NJ, Laín S. Tenovin-D3, a novel small-molecule inhibitor of sirtuin SirT2, increases p21 (CDKN1A) expression in a p53-independent manner. Mol Cancer Ther. 2013 Apr;12(4):352-60. doi: 10.1158/1535-7163.MCT-12-0900. Epub 2013 Jan 15. PubMed PMID: 23322738.

6: Pirrie L, McCarthy AR, Major LL, Morkūnaitė V, Zubrienė A, Matulis D, Lain S, Lebl T, Westwood NJ. Discovery and validation of SIRT2 inhibitors based on tenovin-6: use of a ¹H-NMR method to assess deacetylase activity. Molecules. 2012 Oct 18;17(10):12206-24. doi: 10.3390/molecules171012206. PubMed PMID: 23079492.

7: Lee YL, Peng Q, Fong SW, Chen AC, Lee KF, Ng EH, Nagy A, Yeung WS. Sirtuin 1 facilitates generation of induced pluripotent stem cells from mouse embryonic fibroblasts through the miR-34a and p53 pathways. PLoS One. 2012;7(9):e45633. doi: 10.1371/journal.pone.0045633. Epub 2012 Sep 21. PubMed PMID: 23029150; PubMed Central PMCID: PMC3448677.

8: van Leeuwen IM, Rao B, Sachweh MC, Laín S. An evaluation of small-molecule p53 activators as chemoprotectants ameliorating adverse effects of anticancer drugs in normal cells. Cell Cycle. 2012 May 1;11(9):1851-61. doi: 10.4161/cc.20254. Epub 2012 May 1. PubMed PMID: 22517433; PubMed Central PMCID: PMC3372395.

9: McCarthy AR, Pirrie L, Hollick JJ, Ronseaux S, Campbell J, Higgins M, Staples OD, Tran F, Slawin AM, Lain S, Westwood NJ. Synthesis and biological characterisation of sirtuin inhibitors based on the tenovins. Bioorg Med Chem. 2012 Mar 1;20(5):1779-93. doi: 10.1016/j.bmc.2012.01.001. Epub 2012 Jan 12. PubMed PMID: 22304848.

10: Yuan H, Wang Z, Li L, Zhang H, Modi H, Horne D, Bhatia R, Chen W. Activation of stress response gene SIRT1 by BCR-ABL promotes leukemogenesis. Blood. 2012 Feb 23;119(8):1904-14. doi: 10.1182/blood-2011-06-361691. Epub 2011 Dec 29. PubMed PMID: 22207735; PubMed Central PMCID: PMC3293644.

11: van Leeuwen IM, Higgins M, Campbell J, Brown CJ, McCarthy AR, Pirrie L, Westwood NJ, Laín S. Mechanism-specific signatures for small-molecule p53 activators. Cell Cycle. 2011 May 15;10(10):1590-8. Epub 2011 May 15. PubMed PMID: 21490429.

12: Lain S, Hollick JJ, Campbell J, Staples OD, Higgins M, Aoubala M, McCarthy A, Appleyard V, Murray KE, Baker L, Thompson A, Mathers J, Holland SJ, Stark MJ, Pass G, Woods J, Lane DP, Westwood NJ. Discovery, in vivo activity, and mechanism of action of a small-molecule p53 activator. Cancer Cell. 2008 May;13(5):454-63. doi: 10.1016/j.ccr.2008.03.004. PubMed PMID: 18455128; PubMed Central PMCID: PMC2742717.

13: Brooks CL, Gu W. p53 Activation: a case against Sir. Cancer Cell. 2008 May;13(5):377-8. doi: 10.1016/j.ccr.2008.04.009. PubMed PMID: 18455119; PubMed Central PMCID: PMC2856338.



Additional Information

Related CAS#
1011301-29-3 (Tenovin-6 HCl);
1011557-82-6 (Tenovin-6 free base)