1011557-82-6 Archives - Page 4 of 4 - Amides-buliding-blocks

MacCallum, Stephanie F.’s team published research in Scientific Reports in 3 | CAS: 1011557-82-6

Scientific Reports 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.

MacCallum, Stephanie F. published the artcileDysregulation of autophagy in chronic lymphocytic leukemia with the small-molecule Sirtuin inhibitor Tenovin-6, Recommanded Product: 4-(tert-Butyl)-N-((4-(5-(dimethylamino)pentanamido)phenyl)carbamothioyl)benzamide, the publication is Scientific Reports (2013), 1275, 8 pp., database is CAplus and MEDLINE.

Tenovin-6 (Tnv-6) is a bioactive small mol. 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. Here, we demonstrate that 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. Transcriptomic profiling identified a gene program influenced by Tnv-6 that included autophagy-lysosomal pathway genes. The dysregulation of autophagy was confirmed by changes in cellular ultrastructure and increases in the autophagy-regulatory proteins LC3 (LC3-II) and p62/Sequestosome. Adding bafilomycin-A1, an autophagy inhibitor to Tnv-6 containing cultures did not cause synergistic accumulation of LC3-II, suggesting inhibition of late-stage autophagy by Tnv-6. Thus, in CLL, the cytotoxic effects of Tnv-6 result from dysregulation of protective autophagy pathways.

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

Igase, Masaya’s team published research in Experimental Cell Research in 388 | CAS: 1011557-82-6

Experimental Cell Research 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.

Igase, Masaya published the artcileTenovin-6 induces the SIRT-independent cell growth suppression and blocks autophagy flux in canine hemangiosarcoma cell lines, Category: amides-buliding-blocks, the publication is Experimental Cell Research (2020), 388(1), 111810, database is CAplus and MEDLINE.

Canine hemangiosarcoma (HSA) is a commonly occurring aggressive tumor stemming from the vascular endothelial cells and is considered to be a good model for a similar disease in humans, called angiosarcoma. In this study, we reviewed drug libraries to identify new signal transduction inhibitors that can suppress the cell growth of canine HSA in vitro. We observed that tenovin-6, a sirtuin (SIRT) inhibitor, inhibited cell proliferation and induced cell death in three canine HSA cell lines (JuB4, Re12, and Ud6). These effects were induced through G1 cell cycle arrest and caspase-3 activation. Although tenovin-6 is known as an inhibitor of SIRT1 and SIRT2, knockout (KO) of genes encoding SIRT1 and/or SIRT2 had no apparent impact on cell proliferation in canine HSA. In addition, tenovin-6 showed cell growth inhibition in SIRT KO cells, as well as parental cells. These results indicated the cytotoxicity of tenovin-6 was a SIRT-independent event. Instead, we found that tenovin-6 inhibited autophagy flux in canine HSA cells, as evidenced by the suppression of lysosomal proteolysis. These results suggested that tenovin-6 induces cell growth suppression in canine HSA cells by impairing the lysosomal function. Therefore, tenovin-6 could be used in a new therapeutic strategy to treat canine HSA.

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

Lucera, Mark B.’s team published research in Retrovirology in 14 | CAS: 1011557-82-6

Retrovirology 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, Application of 4-(tert-Butyl)-N-((4-(5-(dimethylamino)pentanamido)phenyl)carbamothioyl)benzamide.

Lucera, Mark B. published the artcileHIV signaling through CD4 and CCR5 activates Rho family GTPases that are required for optimal infection of primary CD4+ T cells, Application of 4-(tert-Butyl)-N-((4-(5-(dimethylamino)pentanamido)phenyl)carbamothioyl)benzamide, the publication is Retrovirology (2017), 4/1-4/13, database is CAplus and MEDLINE.

Background: HIV-1 hijacks host cell machinery to ensure successful replication, including cytoskeletal components for intracellular trafficking, nucleoproteins for pre-integration complex import, and the ESCRT pathway for assembly and budding. It is widely appreciated that cellular post-translational modifications (PTMs) regulate protein activity within cells; however, little is known about how PTMs influence HIV replication. Previously, we reported that blocking deacetylation of tubulin using histone deacetylase inhibitors promoted the kinetics and efficiency of early postentry viral events. To uncover addnl. PTMs that modulate entry and early post-entry stages in HIV infection, we employed a flow cytometric approach to assess a panel of small mol. inhibitors on viral fusion and LTR promoterdriven gene expression. Results: While viral fusion was not significantly affected, early post-entry viral events were modulated by drugs targeting multiple processes including histone deacetylation, methylation, and bromodomain inhibition. Most notably, we observed that inhibitors of the Rho GTPase family of cytoskeletal regulators-including RhoA, Cdc42, and Rho-associated kinase signaling pathways-significantly reduced viral infection. Using phosphoproteomics and a biochem. GTPase activation assay, we found that virion-induced signaling via CD4 and CCR5 activated Rho family GTPases including Rac1 and Cdc42 and led to widespread modification of GTPase signaling-associated factors. Conclusions: Together, these data demonstrate that HIV signaling activates members of the Rho GTPase family of cytoskeletal regulators that are required for optimal HIV infection of primary CD4+ T cells.

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

Eroglu, Zuhal’s team published research in Molecular Medicine Reports in 22 | CAS: 1011557-82-6

Molecular Medicine Reports 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, Safety of 4-(tert-Butyl)-N-((4-(5-(dimethylamino)pentanamido)phenyl)carbamothioyl)benzamide.

Eroglu, Zuhal published the artcileEffect of SIRT1 activators and inhibitors on CD44⁺/CD133⁺-enriched non.small cell lung cancer cells, Safety of 4-(tert-Butyl)-N-((4-(5-(dimethylamino)pentanamido)phenyl)carbamothioyl)benzamide, the publication is Molecular Medicine Reports (2020), 22(1), 575-581, database is CAplus and MEDLINE.

Lung cancer is one of the most commonly diagnosed cancers and it is associated with high rates of morbidity and mortality. Metastasis and relapse of the tumor depend on the survival and proliferation of lung cancer stem cells (LC SCs). The ability to identify CSCs may prevent recurrence and lead to more effective treatments. Sirtuins are a group of deacetylases that include seven variants (SIRT1-7), with sirtuin 1 (SIRT1) being the most intensively investigated. Evidence suggests that SIRT1 is both a tumor-suppressor gene and an oncogene. SIRT1 can deacetylate the tumor-suppressor protein p53 to decrease its activity. SIRT1 activators increase the deacetylation of p53, whereas SIRT1 inhibitors can stimulate p53 by inhibiting deacetylation. In the present study, CD 44⁺ and CD 133⁺-enriched A549 (non-small cell lung cancer) cells collected using the CD 44 and CD 133 CSC surface markers by fluorescence-activated cell sorting method were treated with SIRT1 inhibitors (tenovin-6 and sirtinol) and SIRT1 activators (resveratrol and SRT1720), and their effects on apoptosis, as well as the mRNA and protein expression of SIRT1 and p53 were investigated. Of these agents, it was found that resveratrol increased p53 expression by 4.1-fold, decreased SIRT1 expression by 0.2-fold, and it was the most potent inducer of apoptosis.

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

Moschos, Marilita M.’s team published research in Anticancer Research in 38 | CAS: 1011557-82-6

Anticancer Research 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.

Moschos, Marilita M. published the artcileThe role of historic deacetylase inhibitors in uveal melanoma: current evidence, Recommanded Product: 4-(tert-Butyl)-N-((4-(5-(dimethylamino)pentanamido)phenyl)carbamothioyl)benzamide, the publication is Anticancer Research (2018), 38(7), 3817-3824, database is CAplus and MEDLINE.

A review. Uveal melanoma is the most common intraocular malignancy in adults, representing approx. 3% of all melanoma cases. Despite progress in chemotherapy, radiation and surgical treatment options, the prognosis and survival rates remain poor. Acetylation of historic proteins causes transcription of genes involved in cell growth, DNA replication and progression of cell cycle. Overexpression of histone deacetylases occurs in a wide spectrum of malignancies. Histone deacetylase inhibitors block the action of histone deaceiylases, leading to inhibition of tumor cell proliferation. This article reviewed the potential therapeutic efects of histone deacetylase inhibitors on uveal melanoma. MEDLINE database was used under the key words/phrases: histone deacetylase, inhibitors, uveal melanoma and targeted therapies for uveal melanoma. A total of 47, English articles, not only referring to uveal melanoma, published up to Feb. 2018 were used. Valproic acid, trichostatin A, tenovin-6, depsipeptide, panobinostat (LBH-589), vorinostat (suberanilohydroxamic acid) entinostat (MS-275), quisinostat, NaB, JSL-I, MC/568 and MC1575 are histone deacetylase inhibitors that have demonstrated promising amitumor effects against uveal melanoma. Histone deacetylase inhibitors represent a promising therapeutic approach for the treannent of weal melanoma.

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

Raffa, Demetrio’s team published research in Bioorganic Chemistry in 83 | CAS: 1011557-82-6

Bioorganic 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, Related Products of amides-buliding-blocks.

Raffa, Demetrio published the artcileNovel 4-(3-phenylpropionamido), 4-(2-phenoxyacetamido) and 4-(cinnamamido) substituted benzamides bearing the pyrazole or indazole nucleus: synthesis, biological evaluation and mechanism of action, Related Products of amides-buliding-blocks, the publication is Bioorganic Chemistry (2019), 367-379, database is CAplus and MEDLINE.

Based on some common structural features of known compounds interfering with p53 pathways and our previously synthesized benzamides, we synthesized new Et 5-(4-substituted benzamido)-1-phenyl-1H-pyrazole-4-carboxylates 26a-c, Et 5-(4-substituted benzamido)-1-(pyridin-2-yl)-1H-pyrazole-4-carboxylates 27a-c and N-(1H-indazol-6-yl)-4-substituted benzamides 31a,b bearing in the 4 position of the benzamido moiety the 2-phenylpropanamido or 2-phenoxyacetamido or cinnamamido groups. A preliminary test to evaluate the antiproliferative activity against human lung carcinoma H292 cells highlighted how compound 26c showed the best activity. This last was therefore selected for further studies with the aim to find the mechanism of action. Compound 26c induces intrinsic apoptotic pathway by activating p53 and is also able to activate TRAIL-inducing death pathway by promoting increase of DR4 and DR5 death receptors, downregulation of c-FLIP_L and caspase-8 activation.

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

Walters, Hannah E.’s team published research in Biogerontology in 20 | CAS: 1011557-82-6

Biogerontology 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 C8H6ClF3, Safety of 4-(tert-Butyl)-N-((4-(5-(dimethylamino)pentanamido)phenyl)carbamothioyl)benzamide.

Walters, Hannah E. published the artcileGeneration of a novel model of primary human cell senescence through Tenovin-6 mediated inhibition of sirtuins, Safety of 4-(tert-Butyl)-N-((4-(5-(dimethylamino)pentanamido)phenyl)carbamothioyl)benzamide, the publication is Biogerontology (2019), 20(3), 303-319, database is CAplus and MEDLINE.

Cell senescence, a state of cell cycle arrest and altered metabolism with enhanced pro-inflammatory secretion, underlies at least some aspects of organismal ageing. The sirtuin family of deacetylases has been implicated in preventing premature ageing; sirtuin overexpression or resveratrol-mediated activation of sirtuins increase longevity. Here we show that sirtuin inhibition by short-term, low-dose treatment with the exptl. anti-cancer agent Tenovin-6 (TnV6) induces cellular senescence in primary human fibroblasts. Treated cells cease proliferation and arrest in G1 of the cell cycle, with elevated p21 levels, DNA damage foci, high mitochondrial and lysosomal load and increased senescence-associated β galactosidase activity, together with actin stress fibers and secretion of IL-6 (indicative of SASP upregulation). Consistent with a histone deacetylation role of SIRT1, we find nuclear enlargement, possibly resulting from chromatin decompaction on sirtuin inhibition. These findings highlight TnV6 as a drug that may be useful in clin. settings where acute induction of cell senescence would be beneficial, but also provide the caveat that even supposedly non-genotoxic anticancer drugs can have unexpected and efficacy-limiting impacts on non-transformed cells.

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

Bedalov, A.’s team published research in Methods in Enzymology in 574 | CAS: 1011557-82-6

Methods in Enzymology 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.

Bedalov, A. published the artcileBiology, chemistry, and pharmacology of Sirtuins, Recommanded Product: 4-(tert-Butyl)-N-((4-(5-(dimethylamino)pentanamido)phenyl)carbamothioyl)benzamide, the publication is Methods in Enzymology (2016), 183-211, database is CAplus and MEDLINE.

A review. Sirtuins are a family of protein deacylases related by amino acid sequence and cellular function to the yeast Saccharomyces cerevisiae protein Sir2 (Silent Information Regulator-2), the first of this class of enzymes to be identified and studied in detail. Based on its initially discovered activity, Sir2 was classified as a histone deacetylase that removes acetyl groups from histones H3 and H4. The acetylation/deacetylation of these particular substrates leads to changes in transcriptional silencing at specific loci in the yeast genome, hence its name. Sirtuins, however, have been shown to regulate a wide variety of cellular processes beyond transcriptional repression in varied subcellular compartments and in different cell types. Mechanistically distinct from Zn²⁺-dependent deacylases, sirtuins use NAD as a cofactor in the removal of acetyl and other acyl groups linking metabolic status and posttranslational modification. Sirtuins’ unique position has made them attractive targets for small-mol. drug development. In this chapter, we describe the biol. roles, therapeutic areas in which sirtuins may play a role and development of small-mol. inhibitors of sirtuins employing phenotypic screening technologies ranging from assays in yeast, as well as biochem. screens to yield lead drug development candidates targeting a broad spectrum of human diseases.

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

Bedalov, A.’s team published research in Methods in Enzymology in 574 | CAS: 1011557-82-6

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