Category: 380315-80-0

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, Computed Properties of 380315-80-0, 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 380315-80-0. 380315-80-0 belongs to amides-buliding-blocks, auxiliary class Apoptosis,p53, name is N-((4-Acetamidophenyl)carbamothioyl)-4-(tert-butyl)benzamide, and the molecular formula is C20H23N3O2S, Computed Properties of 380315-80-0.

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

Wilking, Melissa J. published the artcileSirtuin deacetylases: a new target for melanoma management, Formula: C20H23N3O2S, the publication is Cell Cycle (2014), 13(18), 2821-2826, database is CAplus and MEDLINE.

A review. Melanoma continues to cause more deaths than any other skin cancer, necessitating the development of new avenues of treatment. One promising new opportunity comes in the form of mechanism-based therapeutic targets. We recently reported the overexpression and delocalization of the class III histone deacetylase SIRT1 in melanoma, and demonstrated that its small mol. inhibition via Tenovin-1 decreased cell growth and viability of melanoma cells, possibly by a p53 mediated induction of p21. Here, we support our data using addnl. SIRT inhibitors, viz. Sirtinol and Ex-527, which suggests possible benefits of concomitantly inhibiting more than one Sirtuin for an effective cancer management strategy. This “Extra View” paper also includes a discussion of our results in the context of similar recent and concurrent studies. Furthermore, we expand upon our findings in an anal. of new research that may link the cellular localization and growth effects of SIRT1 with the PI3K signaling pathway.

Cell Cycle published new progress about 380315-80-0. 380315-80-0 belongs to amides-buliding-blocks, auxiliary class Apoptosis,p53, name is N-((4-Acetamidophenyl)carbamothioyl)-4-(tert-butyl)benzamide, and the molecular formula is C8H21N3, Formula: C20H23N3O2S.

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

Wilking, Melissa J. published the artcileSIRT1 deacetylase is overexpressed in human melanoma and its small molecule inhibition imparts anti-proliferative response via p53 activation, SDS of cas: 380315-80-0, the publication is Archives of Biochemistry and Biophysics (2014), 94-100, database is CAplus and MEDLINE.

Melanoma causes more deaths than any other skin cancer, and its incidence in the US continues to rise. Current medical therapies are insufficient to control this deadly neoplasm, necessitating the development of new target-based approaches. The objective of this study was to determine the role and functional significance of the class III histone deacetylase SIRT1 in melanoma. We have found that SIRT1 is overexpressed in clin. human melanoma tissues and human melanoma cell lines (Sk-Mel-2, WM35, G361, A375, and Hs294T) compared to normal skin and normal melanocytes, resp. In addition, treatment of melanoma cell lines A375, Hs294T, and G361 with Tenovin-1, a small mol. SIRT1 inhibitor, resulted in a significant decrease in cell growth and cell viability. Further, Tenovin-1 treatment also resulted in a marked decrease in the clonogenic survival of melanoma cells. Further experiments showed that the anti-proliferative response of Tenovin-1 was accompanied by an increase in the protein as well as activity of the tumor suppressor p53. This increase in p53 activity was substantiated by an increase in the protein level of its downstream target p21. Overall, these data suggest that small mol. inhibition of SIRT1 causes anti-proliferative effects in melanoma cells. SIRT1 appears to be acting through the activity of the tumor suppressor p53, which is not mutated in the majority of melanomas. However, future detailed studies are needed to further explore the role and mechanism of SIRT1 in melanoma development and progression and its usefulness in melanoma treatment.

Archives of Biochemistry and Biophysics published new progress about 380315-80-0. 380315-80-0 belongs to amides-buliding-blocks, auxiliary class Apoptosis,p53, name is N-((4-Acetamidophenyl)carbamothioyl)-4-(tert-butyl)benzamide, and the molecular formula is C9H10ClNO2, SDS of cas: 380315-80-0.

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

Ladds, Marcus J. G. W. published the artcileExploitation of dihydroorotate dehydrogenase (DHODH) and p53 activation as therapeutic targets: a case study in polypharmacology, Quality Control of 380315-80-0, the publication is Journal of Biological Chemistry (2020), 295(52), 17935-17949, database is CAplus and MEDLINE.

The tenovins are a frequently studied class of compounds capable of inhibiting sirtuin activity, which is thought to result in increased acetylation and protection of the tumor suppressor p53 from degradation However, as we and other laboratories have shown previously, certain tenovins are also capable of inhibiting autophagic flux, demonstrating the ability of these compounds to engage with more than one target. In this study, we present two addnl. mechanisms by which tenovins are able to activate p53 and kill tumor cells in culture. These mechanisms are the inhibition of a key enzyme of the de novo pyrimidine synthesis pathway, dihydroorotate dehydrogenase (DHODH), and the blockage of uridine transport into cells. These findings hold a 3-fold significance: first, we demonstrate that tenovins, and perhaps other compounds that activate p53, may activate p53 by more than one mechanism; second, that work previously conducted with certain tenovins as SirT1 inhibitors should addnl. be viewed through the lens of DHODH inhibition as this is a major contributor to the mechanism of action of the most widely used tenovins; and finally, that small changes in the structure of a small mol. can lead to a dramatic change in the target profile of the mol. even when the phenotypic readout remains static.

Journal of Biological Chemistry published new progress about 380315-80-0. 380315-80-0 belongs to amides-buliding-blocks, auxiliary class Apoptosis,p53, name is N-((4-Acetamidophenyl)carbamothioyl)-4-(tert-butyl)benzamide, and the molecular formula is C20H23N3O2S, Quality Control of 380315-80-0.

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

McCarthy, Anna R. published the artcileSynthesis and biological characterisation of sirtuin inhibitors based on the tenovins, Application of N-((4-Acetamidophenyl)carbamothioyl)-4-(tert-butyl)benzamide, the publication is Bioorganic & Medicinal Chemistry (2012), 20(5), 1779-1793, database is CAplus and MEDLINE.

The tenovins are small mol. inhibitors of the NAD⁺-dependent family of protein deacetylases known as the sirtuins. There remains considerable interest in inhibitors of this enzyme family due to possible applications in both cancer and neurodegenerative disease therapy. Through the synthesis of novel tenovin analogs, further insights into the structural requirements for activity against the sirtuins in vitro are provided. In addition, the activity of one of the analogs in cells led to an improved understanding of the function of SirT1 in cells.

Bioorganic & Medicinal Chemistry published new progress about 380315-80-0. 380315-80-0 belongs to amides-buliding-blocks, auxiliary class Apoptosis,p53, name is N-((4-Acetamidophenyl)carbamothioyl)-4-(tert-butyl)benzamide, and the molecular formula is C20H23N3O2S, Application of N-((4-Acetamidophenyl)carbamothioyl)-4-(tert-butyl)benzamide.

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

Dhaliwal, Anandika published the artcileEngineering Lineage Potency and Plasticity of Stem Cells using Epigenetic Molecules, Name: N-((4-Acetamidophenyl)carbamothioyl)-4-(tert-butyl)benzamide, the publication is Scientific Reports (2018), 8(1), 1-13, database is CAplus and MEDLINE.

Stem cells are considered as a multipotent regenerative source for diseased and dysfunctional tissues. Despite the promise of stem cells, the inherent capacity of stem cells to convert to tissue-specific lineages can present a major challenge to the use of stem cells for regenerative medicine. We hypothesized that epigenetic regulating mols. can modulate the stem cell’s developmental program, and thus potentially overcome the limited lineage differentiation that human stem cells exhibit based on the source and processing of stem cells. In this study, we screened a library of 84 small mol. pharmacol. agents indicated in nucleosomal modification and identified a sub-set of specific mols. that influenced osteogenesis in human mesenchymal stem cells (hMSCs) while maintaining cell viability in-vitro. Pre-treatment with five candidate hits, Gemcitabine, Decitabine, I-CBP112, Chidamide, and SIRT1/2 inhibitor IV, maximally enhanced osteogenesis in-vitro. In contrast, five distinct mols., 4-Iodo-SAHA, Scriptaid, AGK2, CI-amidine and Delphidine Chloride maximally inhibited osteogenesis. We then tested the role of these mols. on hMSCs derived from aged human donors and report that small epigenetic mols., namely Gemcitabine and Chidamide, can significantly promote osteogenic differentiation by 5.9- and 2.3-fold, resp.

Scientific Reports published new progress about 380315-80-0. 380315-80-0 belongs to amides-buliding-blocks, auxiliary class Apoptosis,p53, name is N-((4-Acetamidophenyl)carbamothioyl)-4-(tert-butyl)benzamide, and the molecular formula is C20H23N3O2S, Name: N-((4-Acetamidophenyl)carbamothioyl)-4-(tert-butyl)benzamide.

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

Ladds, Marcus J. G. W. published the artcileAutophagic flux blockage by accumulation of weakly basic tenovins leads to elimination of B-Raf mutant tumour cells that survive vemurafenib, Related Products of amides-buliding-blocks, the publication is PLoS One (2018), 13(4), e0195956/1-e0195956/21, database is CAplus and MEDLINE.

Tenovin-6 is the most studied member of a family of small mols. with antitumor activity in vivo. Previously, it has been determined that part of the effects of tenovin-6 associate with its ability to inhibit SirT1 and activate p53. However, tenovin-6 has also been shown to modulate autophagic flux. Here we show that blockage of autophagic flux occurs in a variety of cell lines in response to certain tenovins, that autophagy blockage occurs regardless of the effect of tenovins on SirT1 or p53, and that this blockage is dependent on the aliphatic tertiary amine side chain of these mols. Addnl., we evaluate the contribution of this tertiary amine to the elimination of proliferating melanoma cells in culture. We also demonstrate that the presence of the tertiary amine is sufficient to lead to death of tumor cells arrested in G1 phase following vemurafenib treatment. We conclude that blockage of autophagic flux by tenovins is necessary to eliminate melanoma cells that survive B-Raf inhibition and achieve total tumor cell kill and that autophagy blockage can be achieved at a lower concentration than by chloroquine. This observation is of great relevance as relapse and resistance are frequently observed in cancer patients treated with B-Raf inhibitors.

PLoS One published new progress about 380315-80-0. 380315-80-0 belongs to amides-buliding-blocks, auxiliary class Apoptosis,p53, name is N-((4-Acetamidophenyl)carbamothioyl)-4-(tert-butyl)benzamide, and the molecular formula is C20H23N3O2S, Related Products of amides-buliding-blocks.

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

Grbesa, Ivana published the artcileExpression of sirtuin 1 and 2 is associated with poor prognosis in non-small cell lung cancer patients, Computed Properties of 380315-80-0, the publication is PLoS One (2015), 10(4), e0124670/1-e0124670/17, database is CAplus and MEDLINE.

Background: Sirtuin 1 (SIRT1) and sirtuin 2 (SIRT2) are NAD+-dependent protein deacetylases involved in the regulation of key cancer-associated genes. In this study we evaluated the relevance of these deacetylases in lung cancer biol. Material and Methods: Protein levels of SIRT1 and SIRT2 were determined in non-small cell lung cancer (NSCLC) cell lines and primary tumors from 105 patients. Changes in proliferation were assessed after SIRT1 and SIRT2 downregulation in lung cancer cell lines using siRNA-mediated technol. or tenovin-1, a SIRT1 and SIRT2 inhibitor. Results: High SIRT1 and SIRT2 protein levels were found in NSCLC cell lines compared with non-tumor lung epithelial cells. The expression of SIRT1 and SIRT2 proteins was also significantly higher in lung primary tumors than in normal tissue (P<0.001 for both sirtuins). Stronger nuclear SIRT1 staining was observed in adenocarcinomas than in squamous cell carcinomas (P = 0.033). Interestingly, in NSCLC patients, high SIRT1 and SIRT2 expression levels were associated with shorter recurrence-free survival (P = 0.04 and P = 0.007, resp.). Moreover, the combination of high SIRT1 and SIRT2 expression was an independent prognostic factor for shorter recurrence-free survival (P = 0.002) and overall survival (P = 0.022). In vitro studies showed that SIRT1 and/or SIRT2 downregulation significantly decreased proliferation of NSCLC. Conclusions: Our results support the hypothesis that SIRT1 and SIRT2 have a protumorigenic role in lung cancer, promoting cell proliferation. Moreover, the expression of these proteins is associated with poor prognosis in NSCLC patients and may help to identify those NSCLC patients with high risk of recurrence that could benefit from adjuvant therapy after resection.

PLoS One published new progress about 380315-80-0. 380315-80-0 belongs to amides-buliding-blocks, auxiliary class Apoptosis,p53, name is N-((4-Acetamidophenyl)carbamothioyl)-4-(tert-butyl)benzamide, and the molecular formula is C20H23N3O2S, Computed Properties of 380315-80-0.

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

Raza, Shaneabbas published the artcileThe cholesterol metabolite 27-hydroxycholesterol regulates p53 activity and increases cell proliferation via MDM2 in breast cancer cells, Recommanded Product: N-((4-Acetamidophenyl)carbamothioyl)-4-(tert-butyl)benzamide, the publication is Molecular and Cellular Biochemistry (2015), 410(1-2), 187-195, database is CAplus and MEDLINE.

Estrogen is synthesized from cholesterol and high cholesterol levels are suggested to be associated with increased risk of estrogen receptor(ER)-pos. breast cancer. The cholesterol metabolite 27-hydroxycholesterol (27-OHC) was recently identified as a selective estrogen receptor modulator (SERM) and may therefore impact breast cancer progression. However, the mechanisms by which 27-OHC may contribute to breast cancer are not all known. We determined the extent to which 27-OHC regulates cell proliferation in MCF7 ER-pos. breast cancer cell line involving the tumor suppressor protein p53. We found that treatment of MCF7 cells with 27-OHC resulted reduced p53 transcriptional activity. Conversely, treatment of the ER-neg. MDA-MB 231 cells with 27-OHC induced no significant change in p53 activity. Exposure of MCF7 cells to 27-OHC was also associated with increased protein levels of the E3 ubiquitin protein ligase MDM2 and decreased levels of p53. Moreover, 27-OHC also enhanced phys. interaction between p53 and MDM2. Furthermore, 27-OHC-induced proliferation was attenuated using either the p53 activator Tenovin-1 or the MDM2 inhibitor Nutlin-3 and Mdm2 siRNA. Taken together, our results indicate that 27-OHC may contribute to ER-pos. breast cancer progression by disrupting constitutive p53 signaling in an MDM2-dependent manner.

Molecular and Cellular Biochemistry published new progress about 380315-80-0. 380315-80-0 belongs to amides-buliding-blocks, auxiliary class Apoptosis,p53, name is N-((4-Acetamidophenyl)carbamothioyl)-4-(tert-butyl)benzamide, and the molecular formula is C20H23N3O2S, Recommanded Product: N-((4-Acetamidophenyl)carbamothioyl)-4-(tert-butyl)benzamide.

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

Vanheer, Leen N. published the artcileActivity Comparison of Epigenetic Modulators against the Hemoprotozoan Parasites Babesia divergens and Plasmodium falciparum, Related Products of amides-buliding-blocks, the publication is ACS Infectious Diseases (2021), 7(8), 2277-2284, database is CAplus and MEDLINE.

Babesiosis is a tick-borne parasitic disease of humans and livestock that has dramatically increased in frequency and geog. range over the past few decades. Infection of cattle often causes large economic losses, and human infection can be fatal in immunocompromised patients. Unlike for malaria, another disease caused by hemoprotozoan parasites, limited treatment options exist for Babesia infections. As epigenetic regulation is a promising target for new antiparasitic drugs, we screened 324 epigenetic inhibitors against Babesia divergens blood stages and identified 75 (23%) and 17 (5%) compounds that displayed ≥90% inhibition at 10 and 1μM, resp., including over a dozen compounds with activity in the low nanomolar range. We observed differential activity of some inhibitor classes against Babesia divergens and Plasmodium falciparum parasites and identified pairs of compounds with a high difference in activity despite a high similarity in chem. structure, highlighting new insights into the development of epigenetic inhibitors as antiparasitic drugs.

ACS Infectious Diseases published new progress about 380315-80-0. 380315-80-0 belongs to amides-buliding-blocks, auxiliary class Apoptosis,p53, name is N-((4-Acetamidophenyl)carbamothioyl)-4-(tert-butyl)benzamide, and the molecular formula is C5H7N3S3, Related Products of amides-buliding-blocks.

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