Category: 1011557-82-6

Rotili, Dante published the artcileBenzodeazaoxaflavins as Sirtuin Inhibitors with Antiproliferative Properties in Cancer Stem Cells, Recommanded Product: 4-(tert-Butyl)-N-((4-(5-(dimethylamino)pentanamido)phenyl)carbamothioyl)benzamide, the publication is Journal of Medicinal Chemistry (2012), 55(18), 8193-8197, database is CAplus and MEDLINE.

Inhibition of sirtuins has recently been proposed as a promising anticancer strategy. Some of the new benzodeazaoxaflavins (2a, 2b, and 2d) here reported as SIRT1/2 inhibitors were endowed with pro-apoptotic properties in human U937 leukemia cells and, most importantly, together with the prototype MC2141 (1) displayed antiproliferative effects in cancer stem cells from patients with colorectal carcinoma and glioblastoma multiforme, known to be highly tumorigenic, resistant to conventional cancer chemotherapy, and responsible, at least in part, for cancer relapse or recurrence.

Journal of Medicinal Chemistry published new progress about 1011557-82-6. 1011557-82-6 belongs to amides-buliding-blocks, auxiliary class Epigenetics,Sirtuin, name is 4-(tert-Butyl)-N-((4-(5-(dimethylamino)pentanamido)phenyl)carbamothioyl)benzamide, and the molecular formula is C25H34N4O2S, Recommanded Product: 4-(tert-Butyl)-N-((4-(5-(dimethylamino)pentanamido)phenyl)carbamothioyl)benzamide.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Yuan, Hongfeng published the artcileTenovin-6 impairs autophagy by inhibiting autophagic flux, Name: 4-(tert-Butyl)-N-((4-(5-(dimethylamino)pentanamido)phenyl)carbamothioyl)benzamide, the publication is Cell Death & Disease (2017), 8(2), e2608, database is CAplus and MEDLINE.

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.

Cell Death & Disease published new progress about 1011557-82-6. 1011557-82-6 belongs to amides-buliding-blocks, auxiliary class Epigenetics,Sirtuin, name is 4-(tert-Butyl)-N-((4-(5-(dimethylamino)pentanamido)phenyl)carbamothioyl)benzamide, and the molecular formula is C4H10OS, Name: 4-(tert-Butyl)-N-((4-(5-(dimethylamino)pentanamido)phenyl)carbamothioyl)benzamide.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

He, Meilan published the artcileSirtuin 1 and AMPK pathways are essential for the proliferation and survival of primary effusion lymphoma cells, HPLC of Formula: 1011557-82-6, the publication is Journal of Pathology (2017), 242(3), 309-321, database is CAplus and MEDLINE.

Primary effusion lymphoma (PEL) is a rare and aggressive B-cell lymphoma with a dismal prognosis caused by infection of Kaposi’s sarcoma-associated herpesvirus. Despite the findings that numerous viral genes and cellular pathways are essential for the proliferation and survival of PEL cells, there is currently no effective therapeutic treatment for PEL. Here, we report that the metabolic sensor SIRT1 is functionally required for sustaining the proliferation and survival of PEL cells. Knockdown of SIRT1 with specific shRNAs or inhibition of SIRT1 with an inhibitor (tenovin-6) induced cell cycle arrest and apoptosis in PEL cells. We detected high levels of AMPK activation in PEL cells, reflected in AMPKα1 phosphorylation at T174. Knockdown or inhibition of SIRT1 reduced AMPK activation, indicating that SIRT1 was required for AMPK activation. Interestingly, knockdown of AMPK with specific shRNAs or inhibition of AMPK with the inhibitor compound C recapitulated the phenotype of SIRT1, and induced cell cycle arrest and apoptosis, whereas overexpression of a constitutively active AMPK construct rescued the cytotoxic effect of SIRT1 knockdown. Remarkably, treatment with tenovin-6 effectively inhibited the initiation and progression of PEL, and significantly extended the survival of mice in a murine PEL model. Taken together, these results illustrate that the SIRT1-AMPK axis is essential for maintaining the proliferation and survival of PEL and identify SIRT1 and AMPK as potential therapeutic targets, and tenovin-6 as a candidate therapeutic agent for PEL patients.

Journal of Pathology published new progress about 1011557-82-6. 1011557-82-6 belongs to amides-buliding-blocks, auxiliary class Epigenetics,Sirtuin, name is 4-(tert-Butyl)-N-((4-(5-(dimethylamino)pentanamido)phenyl)carbamothioyl)benzamide, and the molecular formula is C25H34N4O2S, HPLC of Formula: 1011557-82-6.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Gan, Na published the artcileHow hydrophilic group affects drug-protein binding modes: Differences in interaction between sirtuins inhibitors Tenovin-1/Tenovin-6 and human serum albumin, Formula: C25H34N4O2S, the publication is Journal of Pharmaceutical and Biomedical Analysis (2021), 114121, database is CAplus and MEDLINE.

Introduction of hydrophilic groups can improve the solubility of leading drugs but inevitably affect their interaction with proteins. This study selected sirtuin inhibitors Tenovin-1 (T1) and Tenovin-6 (T6) as drug models to determine differences in binding mode to human serum albumin (HSA). T1 and T6 quenched the endogenous fluorescence of HSA via static quenching mechanism. Introduction of hydrophilic groups greatly reduced the binding constant, i.e., from 1.302 x 104 L mol-1 for the HSA-T6 system to 0.128 x 104 L mol-1 for the HSA-T1 system. HSA-T1 system was mainly driven by electrostatic interactions while that of HSA-T6 system was hydrophobic interaction and both systems were spontaneous reactions. Site marker experiments and mol. docking indicated that both systems mainly bound to the hydrophobic site I of HSA. Mol. dynamics (MD) simulation anal. further revealed that Tyr148, Tyr150 and Arg257 residues played a key role in this recognition process for both systems. In particular, T6 maintained addnl. several hydrogen bonds with the surrounding residues. T1 had almost no effect on the esterase-like activity of HSA, but T6 inhibited the hydrolysis of p-NPA. Furthermore, differential scanning calorimetry (VP-DSC), CD (CD) and Fourier transform IR (FTIR) spectroscopy confirmed that HSA in the T6 system undergone a more significant conformational transition than that in the T1 system.

Journal of Pharmaceutical and Biomedical Analysis published new progress about 1011557-82-6. 1011557-82-6 belongs to amides-buliding-blocks, auxiliary class Epigenetics,Sirtuin, name is 4-(tert-Butyl)-N-((4-(5-(dimethylamino)pentanamido)phenyl)carbamothioyl)benzamide, and the molecular formula is C25H34N4O2S, Formula: C25H34N4O2S.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Smith, Kirk published the artcileMetabolic signatures of regulation by phosphorylation and acetylation, Recommanded Product: 4-(tert-Butyl)-N-((4-(5-(dimethylamino)pentanamido)phenyl)carbamothioyl)benzamide, the publication is iScience (2022), 25(1), 103730, database is CAplus and MEDLINE.

Acetylation and phosphorylation are highly conserved posttranslational modifications (PTMs) that regulate cellular metabolism, yet how metabolic control is shared between these PTMs is unknown. Here we analyze transcriptome, proteome, acetylome, and phosphoproteome datasets in E. coli, S. cerevisiae, and mammalian cells across diverse conditions using CAROM, a new approach that uses genome-scale metabolic networks and machine learning to classify targets of PTMs. We built a single machine learning model that predicted targets of each PTM in a condition across all three organisms based on reaction attributes (AUC>0.8). Our model predicted phosphorylated enzymes during a mammalian cell-cycle, which we validate using phosphoproteomics. Interpreting the machine learning model using game theory uncovered enzyme properties including network connectivity, essentiality, and condition-specific factors such as maximum flux that differentiate targets of phosphorylation from acetylation. The conserved and predictable partitioning of metabolic regulation identified here between these PTMs may enable rational rewiring of regulatory circuits.

iScience published new progress about 1011557-82-6. 1011557-82-6 belongs to amides-buliding-blocks, auxiliary class Epigenetics,Sirtuin, name is 4-(tert-Butyl)-N-((4-(5-(dimethylamino)pentanamido)phenyl)carbamothioyl)benzamide, and the molecular formula is C5H5NO3S, Recommanded Product: 4-(tert-Butyl)-N-((4-(5-(dimethylamino)pentanamido)phenyl)carbamothioyl)benzamide.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Eto, Shotaro published the artcileAnti-tumor effects of the histone deacetylase inhibitor vorinostat on canine urothelial carcinoma cells, HPLC of Formula: 1011557-82-6, the publication is PLoS One (2019), 14(6), e0218382, database is CAplus and MEDLINE.

Canine urothelial carcinoma (cUC) is the most common tumor of the lower urinary tract in dogs. Although chemotherapy and radical surgery have improved the overall survival, most dogs with cUC succumb to metastasis or recurrence. Therefore, the development of an effective systematic therapy is warranted. In this study, a comprehensive drug screening test using a cUC cell line was performed and the anti-tumor effect of a histone deacetylase (HDAC) inhibitor was evaluated. Comprehensive drug screening was performed on cUC cells. Based on this screening, the anti-proliferation effect of vorinostat, an HDAC inhibitor clin. applied in humans, was evaluated using several cUC cell lines in sulforhodamine B and flow cytometry assays. Western blot anal. was also performed to evaluate the degree of acetylation of histone H3 as well as the expression and phosphorylation of cell cycle-related mols. The anti-tumor effect of vorinostat in vivo was evaluated using a xenograft model. Finally, immunohistochem. was performed on acetyl-histone H3 in cUC and the relationship between the degree of acetylation and prognosis was examined using Kaplan-Meier survival anal. Drug screening revealed that HDAC inhibitors consistently inhibited the growth of cUC cells. Vorinostat inhibited the growth of 6 cUC cell lines in a dose-dependent manner and induced G0/G1 cell cycle arrest. Western blot anal. showed that vorinostat mediated the acetylation of histone H3, the dephosphorylation of p-Rb, and the upregulation of p21 upon exposure to vorinostat. Furthermore, inhibition of tumor growth was observed in the xenograft model. In clin. cUC cases, neoplastic urothelium showed significant deacetylation of histones compared to the normal control, where lower histone acetylation levels were associated with a poor prognosis. In conclusion, the therapeutic potential of vorinostat was demonstrated in cUC. Histone deacetylation may be related to cUC tumor progression.

PLoS One published new progress about 1011557-82-6. 1011557-82-6 belongs to amides-buliding-blocks, auxiliary class Epigenetics,Sirtuin, name is 4-(tert-Butyl)-N-((4-(5-(dimethylamino)pentanamido)phenyl)carbamothioyl)benzamide, and the molecular formula is C25H34N4O2S, HPLC of Formula: 1011557-82-6.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Medda, Federico published the artcileNovel Cambinol Analogs as Sirtuin Inhibitors: Synthesis, Biological Evaluation, and Rationalization of Activity, Category: amides-buliding-blocks, the publication is Journal of Medicinal Chemistry (2009), 52(9), 2673-2682, database is CAplus and MEDLINE.

The tenovins and cambinol are two classes of sirtuin inhibitor that exhibit antitumor activity in preclin. models. This report describes modifications to the core structure of cambinol, in particular by incorporation of substituents at the N1-position, which lead to increased potency and modified selectivity. These improvements have been rationalized using mol. modeling techniques. The expected functional selectivity in cells was also observed for both a SIRT1 and a SIRT2 selective analog.

Journal of Medicinal Chemistry published new progress about 1011557-82-6. 1011557-82-6 belongs to amides-buliding-blocks, auxiliary class Epigenetics,Sirtuin, name is 4-(tert-Butyl)-N-((4-(5-(dimethylamino)pentanamido)phenyl)carbamothioyl)benzamide, and the molecular formula is C25H34N4O2S, Category: amides-buliding-blocks.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Spiegelman, Nicole A. published the artcileDirect Comparison of SIRT2 Inhibitors: Potency, Specificity, Activity-Dependent Inhibition, and On-Target Anticancer Activities, COA of Formula: C25H34N4O2S, the publication is ChemMedChem (2018), 13(18), 1890-1894, database is CAplus and MEDLINE.

Sirtuin inhibitors have attracted much interest due to the involvement of sirtuins in various biol. processes. Several SIRT2-selective inhibitors have been developed, and some exhibit anticancer activities. To facilitate the choice of inhibitors in future studies and the development of better inhibitors, the authors directly compared several reported SIRT2-selective inhibitors: AGK2, SirReal2, Tenovin-6, and TM. In vitro, TM is the most potent and selective inhibitor, and only TM could inhibit the demyristoylation activity of SIRT2. SirReal2, Tenovin-6, and TM all showed cytotoxicity in cancer cell lines, with Tenovin-6 being the most potent, but only TM showed cancer-cell-specific toxicity. All four compounds inhibited the anchorage-independent growth of HCT116 cells, but the effect of TM was most significantly affected by SIRT2 overexpression, suggesting that the anticancer effect of TM depends more on SIRT2 inhibition. These results not only provide useful guidance about choosing the right SIRT2 inhibitor in future studies, but also suggest general practices that should be followed for small-mol. inhibitor development activities.

ChemMedChem published new progress about 1011557-82-6. 1011557-82-6 belongs to amides-buliding-blocks, auxiliary class Epigenetics,Sirtuin, name is 4-(tert-Butyl)-N-((4-(5-(dimethylamino)pentanamido)phenyl)carbamothioyl)benzamide, and the molecular formula is C14H12N2S, COA of Formula: C25H34N4O2S.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

van Leeuwen, Ingeborg M. M. published the artcileAn evaluation of small-molecule p53 activators as chemoprotectants ameliorating adverse effects of anticancer drugs in normal cells, SDS of cas: 1011557-82-6, the publication is Cell Cycle (2012), 11(9), 1851-1861, database is CAplus and MEDLINE.

Pharmacol. activation of wild-type p53 has been found to protect normal cells in culture from cytotoxicity and nuclear aberrations caused by conventional cancer therapeutics. Hence, small-mol. p53 activators could have clin. benefits as chemoprotectants for cancer patients bearing p53-mutant tumors. We have evaluated 16 p53-based cyclotherapy regimes combining p53 activators tenovin-6, leptomycin B, nutlin-3 and low dose actinomycin D, with clin. utilized chemotherapeutic agents (S- and M-phase poisons) vinblastine, vinorelbine, cytosine arabinoside and gemcitabine. All the p53 activators induce reversible cell cycle arrest in primary human fibroblasts and protect them from both S- and M-phase poisons. Furthermore, studies with p53-mutant cancer cell lines show that nutlin-3 and low-dose actinomycin D do not affect the sensitivity of these cells to any of the chemotherapeutics tested. Thus, these two small mols. could be suitable choices for cyclotherapy regimes involving S- or M-phase poisons. In contrast, pre-incubation of p53-mutant cells with tenovin-6 or leptomycin B reduces the efficacy of vinca alkaloids, suggesting that these p53 activators could be effective as chemoprotectants if combined with S- but not M-phase poisons. Discrepancies were observed between the levels of protection detected immediately after treatment and following recovery in fresh medium. This highlights the need to assess both short- and long-term effects when evaluating compounds as potential chemoprotectants for cancer therapy.

Cell Cycle published new progress about 1011557-82-6. 1011557-82-6 belongs to amides-buliding-blocks, auxiliary class Epigenetics,Sirtuin, name is 4-(tert-Butyl)-N-((4-(5-(dimethylamino)pentanamido)phenyl)carbamothioyl)benzamide, and the molecular formula is C25H47NO8, SDS of cas: 1011557-82-6.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Nielsen, Alexander L. published the artcileMechanism-based inhibitors of SIRT2: structure-activity relationship, X-ray structures, target engagement, regulation of α-tubulin acetylation and inhibition of breast cancer cell migration, Name: 4-(tert-Butyl)-N-((4-(5-(dimethylamino)pentanamido)phenyl)carbamothioyl)benzamide, the publication is RSC Chemical Biology (2021), 2(2), 612-626, database is CAplus and MEDLINE.

Sirtuin 2 (SIRT2) is a protein deacylase enzyme that removes acetyl groups and longer chain acyl groups from post-translationally modified lysine residues. It affects diverse biol. functions in the cell and has been considered a drug target in relation to both neurodegenerative diseases and cancer. Therefore, access to well-characterized and robust tool compounds is essential for the continued investigation of the complex functions of this enzyme. Here, we report a collection of chem. probes that are potent, selective, stable in serum, water-soluble, and inhibit SIRT2-mediated deacetylation and demyristoylation in cells. Compared to the current landscape of SIRT2 inhibitors, this is a unique ensemble of features built into a single compound We expect the developed chemotypes to find broad application in the interrogation of SIRT2 functions in both healthy and diseased cells, and to provide a foundation for the development of future therapeutics.

RSC Chemical Biology published new progress about 1011557-82-6. 1011557-82-6 belongs to amides-buliding-blocks, auxiliary class Epigenetics,Sirtuin, name is 4-(tert-Butyl)-N-((4-(5-(dimethylamino)pentanamido)phenyl)carbamothioyl)benzamide, and the molecular formula is C25H34N4O2S, Name: 4-(tert-Butyl)-N-((4-(5-(dimethylamino)pentanamido)phenyl)carbamothioyl)benzamide.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics