Category: 380315-80-0

Christensen, Matthew D. published the artcileAn inhibitor screen identifies histone-modifying enzymes as mediators of polymer-mediated transgene expression from plasmid DNA, Recommanded Product: N-((4-Acetamidophenyl)carbamothioyl)-4-(tert-butyl)benzamide, the publication is Journal of Controlled Release (2018), 210-223, database is CAplus and MEDLINE.

Effective transgene expression in mammalian cells relies on successful delivery, cytoplasmic trafficking, and nuclear translocation of the delivered vector, but delivery is impeded by several formidable physicochem. barriers on the surface of and within the target cell. Although methods to overcome cellular exclu. and endosomal entrap. have been studied extensively, strategies to overcome ineffi. nuclear entry and subseq. intranuclear barriers to effec. transient gene expre. have only been sparsely explored. In particular, the role of nuclear packaging of DNA with histone proteins. In this work, a parallel screen of small mol. inhibitors of chromatin-modifying enzy. resulted in the identifi. of class I/II HDACs, sirtuins, LSD1, HATs, and the methyltransferases EZH2 and MLL as targets whose inhibi. led to the enhanc. of transgene expre. following polymer-mediated delivery of plasmid DNA. Quant. PCR studies revealed that HDAC inhibi. enhances the amount of plasmid DNA delivered to the nucleus in UMUC3 human bladder cancer cells. N-ChIP-qPCR experiments in CHO-K1 cells indicated that plasmids indeed interact with intracellular core Histone H3, and inhibitors of HDAC and LSD1 proteins. Pair-wise treatments of effective inhibitors led to synergistic enhanc. of transgene expression to varying extents in both cell types. Our results demonstrate that the ability to modulate enzy. that play a role in epigenetic processes can enhance the efficacy of non-viral gene delivery.

Journal of Controlled Release 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

Marx, Christian published the artcileThe sirtuin 1/2 inhibitor tenovin-1 induces a nonlinear apoptosis-inducing factor-dependent cell death in a p53 null Ewing’s sarcoma cell line, HPLC of Formula: 380315-80-0, the publication is Investigational New Drugs (2018), 36(3), 396-406, database is CAplus and MEDLINE.

The sirtuin 1/2 inhibitor tenovin-1 activates p53 and may have potential in the management of cancer. Here, we investigated the responsiveness of Ewing’s sarcoma cells to tenovin-1. We examined its effects in two Ewing’s sarcoma cell lines with different p53 status, i.e. in p53 wild-type and p53 null cells. Effects were assessed by flow cytometric analyses of cell death, mitochondrial membrane depolarization and reactive oxygen species (ROS) generation, by caspase 3/7 activity measurement, by mRNA expression profiling and by immunoblotting. Tenovin-1 elicited caspase-mediated cell death in p53 wild-type cells, but caspase-independent cell death in p53 null cells. Remarkably, it induced a nonlinear concentration response in the latter: low concentrations of tenovin-1 were much more effective than were higher concentrations Tenovin-1’s effects in p53 null cells involved gene expression changes of Bcl-2 family members, mitochondrial membrane depolarization, nuclear translocation of apoptosis-inducing factor, ROS formation and DNA damage; all these effects followed a bell-shaped pattern. In conclusion, our results provide new insights into tenovin-1’s mode of action by demonstrating that it can induce different pathways of cell death.

Investigational New Drugs 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, HPLC of Formula: 380315-80-0.

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

Marx-Blumel, Lisa published the artcileAssessment of HDACi-induced cytotoxicity, Computed Properties of 380315-80-0, the publication is Methods in Molecular Biology (New York, NY, United States) (2017), 23-45, database is CAplus and MEDLINE.

A review. The chromatin contains the genetic and the epigenetic information of a eukaryotic organism. Posttranslational modifications of histones, such as acetylation and methylation, regulate their structure and control gene expression. Histone acetyltransferases (HATs) acetylate lysine residues in histones while histone deacetylases (HDACs) remove this modification. HDAC inhibitors (HDACi) can alter gene expression patterns and induce cytotoxicity in cancer cells. Here we provide an overview of methods to determine the cytotoxic effects of HDACi treatment. Our chapter describes colorimetric methods, like trypan blue exclusion test, crystal violet staining, lactate dehydrogenase assay, MTT and Alamar Blue assays, as well as fluorogenic methods like TUNEL staining and the caspase-3/7 activity assay. Moreover, we summarize flow cytometric anal. of propidium iodide uptake, annexin V staining, cell cycle status, ROS levels, and mitochondrial membrane potential as well as detection of apoptosis by Western blot.

Methods in Molecular Biology (New York, NY, United States) 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

Sonnemann, J. published the artcilep53-dependent and p53-independent anticancer effects of different histone deacetylase inhibitors, Application of N-((4-Acetamidophenyl)carbamothioyl)-4-(tert-butyl)benzamide, the publication is British Journal of Cancer (2014), 110(3), 656-667, database is CAplus and MEDLINE.

Background: Histone deacetylase inhibitors (HDACi) are promising antineoplastic agents, but their precise mechanisms of actions are not well understood. In particular, the relevance of p53 for HDACi-induced effects has not been fully elucidated. We investigated the anticancer effects of four structurally distinct HDACi, vorinostat, entinostat, apicidin and valproic acid, using isogenic HCT-116 colon cancer cell lines differing in p53 status. Methods: Effects were assessed by MTT assay, flow-cytometric analyses of propidium iodide uptake, mitochondrial depolarisation and cell-cycle distribution, as well as by gene expression profiling. Results: Vorinostat was equally effective in p53 wild-type and null cells, whereas entinostat was less effective in p53 null cells. Histone deacetylase inhibitors treatment suppressed the expression of MDM2 and increased the abundance of p53. Combination treatments showed that vorinostat enhanced the cytotoxic activity of TRAIL and bortezomib, independent of the cellular p53 status. Investigations into the effects of an inhibitor of the sirtuin class of HDAC, tenovin-1, revealed that tenovin-1-mediated cell death hinged on p53. Conclusion: These results demonstrate that vorinostat activates p53, but does not require p53 for inducing its anticancer action. Yet they also demonstrate that entinostat-induced cytotoxic effects partially depend on p53, indicating that different HDACi have a different requirement for p53.

British Journal of Cancer 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 C23H43NP2, Application of N-((4-Acetamidophenyl)carbamothioyl)-4-(tert-butyl)benzamide.

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

Chen, Enjiang published the artcilemiR-26b enhances the sensitivity of hepatocellular carcinoma to Doxorubicin via USP9X-dependent degradation of p53 and regulation of autophagy, SDS of cas: 380315-80-0, the publication is International Journal of Biological Sciences (2021), 17(3), 781-795, database is CAplus and MEDLINE.

Multi-drug resistance is a major challenge to hepatocellular carcinoma (HCC) treatment, and the over-expression or deletion of microRNA (miRNA) expression is closely related to the drug-resistant properties of various cell lines. However, the underlying mol. mechanisms remain unclear. CCK-8, EdU, flow cytometry, and transmission electron microscopy were performed to determine cell viability, proliferation, apoptosis, autophagic flow, and nanoparticle characterization, resp. In this study, the results showed that the expression of miR-26b was downregulated following doxorubicin treatment in human HCC tissues. An miR-26b mimic enhanced HCC cell doxorubicin sensitivity, except in the absence of p53 in Hep3B cells. Delivery of the proteasome inhibitor, MG132, reversed the inhibitory effect of miR-26b on the level of p53 following doxorubicin treatment. Tenovin-1 (an MDM2 inhibitor) protected p53 from ubiquitination-mediated degradation only in HepG2 cells with wild type p53. Tenovin-1 pretreatment enhanced HCC cell resistance to doxorubicin when transfected with an miR-26b mimic. Moreover, the miR-26b mimic inhibited doxorubicin-induced autophagy and the autophagy inducer, rapamycin, eliminated the differences in the drug sensitivity effect of miR-26b. In vivo, treatment with sp94dr/miR-26b mimic nanoparticles plus doxorubicin inhibited tumor growth. Our current data indicate that miR-26b enhances HCC cell sensitivity to doxorubicin through diminishing USP9X-mediated p53 de-ubiquitination caused by DNA damaging drugs and autophagy regulation. This miRNA-mediated pathway that modulates HCC will help develop novel therapeutic strategies.

International Journal of Biological Sciences 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, SDS of cas: 380315-80-0.

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

Xiao, Qing published the artcileIncreased expression of Sonic hedgehog restores diabetic endothelial progenitor cells and improves cardiac repair after acute myocardial infarction in diabetic mice, Application of N-((4-Acetamidophenyl)carbamothioyl)-4-(tert-butyl)benzamide, the publication is International Journal of Molecular Medicine (2019), 44(3), 1091-1105, database is CAplus and MEDLINE.

Investigated whether Shh revitalized diabetic EPCs and consequently improved the deteriorative status of DMI. Apoptosis, cell function, and protein expression were investigated in EPCs in vitro. First, the in vitro results demonstrated that the apoptosis of diabetic EPCs was reduced following treatment with Shh protein for 24 h, under normal or hypoxic conditions. Bmi1, an antiapoptotic protein found in several cells, was reduced in diabetic EPCs under normal or hypoxic conditions, but was upregulated after Shh protein stimulation. When Bmi1-siRNA was administered, the antiapoptotic effect of Shh was significantly reversed. In addition, p53, a Bmi1-targeted gene, was demonstrated to mediate the antiapoptotic effect of the Shh/Bmi1 pathway in diabetic EPCs. The Shh/Bmi1/p53 axis also enhanced the diabetic EPC function. In vivo, Shh-modified diabetic EPCs exhibited increased EPC retention and decreased apoptosis at 3 days post-DMI. At 14 days post-DMI, these cells presented enhanced capillary d., reduced myocardial fibrosis and improved cardiac function. In conclusion, the present results demonstrated that the Shh pathway restored diabetic EPCs through the Shh/Bmi1/p53 axis, suppressed myocardial apoptosis and improved myocardial angiogenesis, thus reducing cardiac fibrosis and finally restoring myocardial repair and cardiac function in DMI. Thus, the Shh pathway may serve as a potential target for autologous cell therapy in diabetic myocardial ischemia.

International Journal of Molecular Medicine 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 C13H10O2, Application of N-((4-Acetamidophenyl)carbamothioyl)-4-(tert-butyl)benzamide.

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

Ibrahim, Ayon published the artcileLocal Mitochondrial ATP Production Regulates Endothelial Fatty Acid Uptake and Transport, Name: N-((4-Acetamidophenyl)carbamothioyl)-4-(tert-butyl)benzamide, the publication is Cell Metabolism (2020), 32(2), 309-319.e7, database is CAplus and MEDLINE.

Most organs use fatty acids (FAs) as a key nutrient, but little is known of how blood-borne FAs traverse the endothelium to reach underlying tissues. We conducted a small-mol. screen and identified niclosamide as a suppressor of endothelial FA uptake and transport. Structure/activity relationship studies demonstrated that niclosamide acts through mitochondrial uncoupling. Inhibitors of oxidative phosphorylation and the ATP/ADP translocase also suppressed FA uptake, pointing principally to ATP production Decreasing total cellular ATP by blocking glycolysis did not decrease uptake, indicating that specifically mitochondrial ATP is required. Endothelial FA uptake is promoted by fatty acid transport protein 4 (FATP4) via its ATP-dependent acyl-CoA synthetase activity. Confocal microscopy revealed that FATP4 resides in the endoplasmic reticulum (ER), and that endothelial ER is intimately juxtaposed with mitochondria. Together, these data indicate that mitochondrial ATP production, but not total ATP levels, drives endothelial FA uptake and transport via acyl-CoA formation in mitochondrial/ER microdomains.

Cell Metabolism 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

Wu, Shan published the artcileConnexin 32 deficiency protects the liver against ischemia/reperfusion injury, Computed Properties of 380315-80-0, the publication is European Journal of Pharmacology (2020), 173056, database is CAplus and MEDLINE.

Hepatic ischemia/reperfusion (I/R) injury is a common complication in the clin. setting. Our previous study has shown that connexin 32 (Cx32) plays a major role in renal I/R injury; however, the role of Cx32 in hepatic I/R injury remains unknown. Liver tissue and serum samples from patients undergoing orthotopic liver transplantation (OLT) were used to evaluate the function of Cx32 in OLT post-reperfusion injury. Then, partial hepatic ischemia was established in global Cx32 knockout mice and wild-type mice followed by reperfusion. Hepatic injury markers were examined Cx32 small interfering RNA and the p53 inhibitor, pifithrin-α, tenovin-1 were used to examine the relationship between Cx32 and the p53/puma pathways in the BRL-3A and murine primary hepatocytes hypoxia/reoxygenation (H/R) model. Corresponding to liver damage, Cx32 was significantly induced both during OLT in human patients and partial hepatic I/R in mice. Cx32 KO mice exhibited less liver injury than controls. Cx32 deficiency significantly suppressed the p53/puma pathways and hepatocyte apoptosis. Similar results were observed in the BRL-3A and murine primary hepatocytes H/R model. Propofol protected against OLT post-reperfusion injury and hepatocyte apoptosis by inhibiting Cx32. In conclusion Cx32 is a novel regulator of hepatic I/R injury through the modulation of hepatocyte apoptosis and damage, largely via the p53/puma signaling pathway.

European Journal of Pharmacology 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 C24H29N5O3, Computed Properties of 380315-80-0.

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

Wan, Yihong published the artcileTenovin-1 inhibited dengue virus replication through SIRT2, Name: N-((4-Acetamidophenyl)carbamothioyl)-4-(tert-butyl)benzamide, the publication is European Journal of Pharmacology (2021), 174264, database is CAplus and MEDLINE.

Dengue fever is a common arbovirus disease, which has been spread to the entire tropical world. At present, effective drugs for the treatment of dengue fever have not yet appeared, and the dengue vaccines studied in various countries have also experienced severe adverse reactions. Thus it is urgent to find new chems. against dengue virus. Now we found Sirtuins (SIRTs) were increased during dengue virus infection and tenovin-1, a SIRT1/2 inhibitor, showed an impressive antiviral ability in vitro. In BHK-21 cells, tenovin-1 inhibited the replication of DENV2 with an EC50 at 3.41 ± 1.10μM, also inhibited other three types of dengue viruses with EC50 at 0.97 ± 1.11μM, 1.81 ± 1.08μM, 3.81 ± 1.34μM resp. Moreover, the cytopathic effect-induced DENV2 was largely improved by tenovin-1 treatment and the release of progeny viruses was inhibited by tenovin-1 treatment. At the same time, the viral protein level and mRNA level were decreased with tenovin-1 treatment after dengue virus infection. From the drug-addition assay, the tenovin-1 played its antiviral after viral infection, which indicated tenovin-1 was not a microbicide. Apart from its antiviral effect, tenovin-1 inhibited the inflammatory response caused by DENV2, reducing the release of inflammatory factors during viral infection. The antiviral effect of tenovin-1 was abrogated with SIRT agonist or SIRT2 knockdown treatment, which indicated the effect of tenovin-1 was on-target. In conclusion, tenovin-1 was proved to be a promising compound against flavivirus infection through SIRT2, which should be pay more attention for further study.

European Journal of Pharmacology 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 C5H6BNO2, Name: N-((4-Acetamidophenyl)carbamothioyl)-4-(tert-butyl)benzamide.

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

Alcain, Francisco J. published the artcileSirtuin inhibitors, Recommanded Product: N-((4-Acetamidophenyl)carbamothioyl)-4-(tert-butyl)benzamide, the publication is Expert Opinion on Therapeutic Patents (2009), 19(3), 283-294, database is CAplus and MEDLINE.

A review. Background: The sirtuin family of deacetylase enzymes comprises seven proteins (SIRT1-7) that are dependent on NAD⁺ for their activity. Three proteins are located in the nucleus, three in the mitochondria and only one is predominantly cytoplasmic. Caloric restriction and oxidative stress generally up-regulate their expression. SIRT1, the ortholog of yeast Sir2, is the mammalian sirtuin that has been most extensively studied to date. Among other targets, SIRT1 down-regulates the activity of the nuclear transcription factor p53, being this related with an increase in lifespan and cell survival associated to stress resistance. Objective: Because sirtuin modulation could have beneficial effects on several human diseases, there is a growing interest in the discovery and development of small mols. that modify its activity. This review will be focused on sirtuin inhibitors. Conclusions: Several specific inhibitors of SIRT1 have been described. These compounds could be mainly useful for the treatment of cancers by increasing p53 activity that stops the formation of tumors and induces apoptosis. A p53-independent massive induction of apoptosis has been also described for one inhibitor. In addition, a potent and selective SIRT2 inhibitor that ameliorates the α-synuclein fibril formation in Parkinson disease has been proposed to treat this kind of neurodegenerative disease.

Expert Opinion on Therapeutic Patents 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