Tag: M.W=350-400

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

Patil, Vijay published the artcileRMAC study: A randomized study for evaluation of metronomic adjuvant chemotherapy in recurrent head and neck cancers post salvage surgical resection in those who are ineligible for re-irradiation, Name: 4-(5-(p-Tolyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide, the publication is Oral Oncology (2022), 105816, database is CAplus and MEDLINE.

Adjuvant re-chemoradiation after salvage surgery improves disease-free survival in recurrent head and neck cancer. However, most patients are ineligible for re-irradiation and are kept on observation. We investigated the efficacy of metronomic adjuvant chemotherapy (MAC) in this group of patients compared to observation. This was a randomized integrated phase II/III clin. trial. Adults with recurrent head and neck cancer, who had undergone salvage surgery, but were ineligible for adjuvant re-irradiation were randomized in a 1:1 ratio to either MAC arm or observation. MAC consisted of weekly oral methotrexate (at a dose of 15 mg per square meter of body surface area) and celecoxib (at a dose of 200 mg orally twice daily) for 6 mo. The primary endpoint of phase 2 was disease-free survival (DFS) while that of phase 3 was overall survival (OS). For phase 2, to detect an improvement in the hazard ratio (HR) 0.67 with MAC, with a type 1 error of 10% (1-sided), type 2 error of 30%, 105 patients were required. While for phase 3, with a target HR of 0.77, with a type 1 error of 5%, type 2 error of 20%, 318 patients were required. Here we report the results of phase 2 part of the study.At a median follow up of 30.2 mo (95% confidence interval (CI), 25.3 to 35.1) the 1 yr and 2-yr DFS were 57.4% (95% CI, 42.8-69.5) and 37.6% (95% CI, 24.1-51) in MAC arm whereas the corresponding numbers were 62.3% (95% CI, 47.8 to 73.8) and 54.2%(95% CI, 39.8 to 66.5) in observation arm, resp. (hazard ratio for progression, 1.45; 95% CI, 0.87 to 2.47; P = 0.15). In the MAC arm, the 1 and 2 yr OS was 78.7% (95% CI, 64.9 to 87.6) and 48% (95% CI, 34.1 to 62). The corresponding figures in the observation arm were 79.2% (95% CI, 65.7 to 87.9) and 65.5% (95% CI, 50.9 to 76.7) (hazard ratio for death, 1.7, 95% CI, 0.94 to 3.08; P = 0.08). The adjuvant 6-mo metronomic schedule was ineffective in improving outcomes in recurrent head and neck cancers post salvage surgery who are ineligible for re-radiation.Trial registration.

Oral Oncology published new progress about 169590-42-5. 169590-42-5 belongs to amides-buliding-blocks, auxiliary class Sulfamide,Immunology/Inflammation,COX, name is 4-(5-(p-Tolyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide, and the molecular formula is C17H14F3N3O2S, Name: 4-(5-(p-Tolyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide.

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

Badalanloo, Kimia published the artcileCytotoxic and Apoptotic Effects of Celecoxib and Topotecan on AGS and HEK 293 Cell Lines, Category: amides-buliding-blocks, the publication is Journal of Gastrointestinal Cancer (2022), 53(1), 99-104, database is CAplus and MEDLINE.

Abstract: Purpose: This study is aimed to assess the anti-cancer effects of Celecoxib and topotecan against Human Gastric cancer cell line (AGS) in comparison to the control in an in-vitro study. Methods: In this exptl. study, Celecoxib and topotecan was prepared at concentrations of 500, 250, 125, 62.5, 31.2, 15.6 and 7.8 mg/mL. The effect of celecoxib and topotecan sep. and in mixed form were investigated on AGS and normal HEK cells. To investigate the cell survival, MTT method was used to study the pathway of apoptosis using flowcytometry and Caspase kits based on colorimetric. Finally, one-way ANOVA and t-test were used to analyze the data. Results: The results of this study indicated that Celecoxib was cytotoxic against AGS and HEK cell lines. The topotecan indicated a significant cytotoxicity against AGS cells and was not toxic against HEK cell line. Our results indicated that Celecoxib and topotecan have synergist effects against AGS and HEK cell lines and were more effective than sep. celecoxib or topotecan. Conclusion: The mixture of clecoxib and topotecan was more effective than celecoxib and topotecan in sep. form. Our results indicated that use mixed forms of treatments can cause excellent therapeutic effects and can cause less side effects.

Journal of Gastrointestinal Cancer published new progress about 169590-42-5. 169590-42-5 belongs to amides-buliding-blocks, auxiliary class Sulfamide,Immunology/Inflammation,COX, name is 4-(5-(p-Tolyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide, and the molecular formula is C17H14F3N3O2S, Category: amides-buliding-blocks.

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

Mashal, Mohammad Shafiq published the artcileSimultaneous quantification of 19 nonsteroidal anti-inflammatory drugs in oral fluid by liquid chromatography-high resolution mass spectrometry: Application on ultratrail runners oral fluid, Application of 4-(5-(p-Tolyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide, the publication is Drug Testing and Analysis (2022), 14(4), 701-712, database is CAplus and MEDLINE.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are a therapeutic class suspected to be used by ultratrail runners. The use of NSAIDs during ultratrails is known to be associated with various adverse effects. To study the prevalence of NSAIDs intake in ultratrail runners, oral fluid (OF) is a relevant matrix as it is noninvasive and easy to collect. The aim of our work was to develop and validate a liquid-liquid extraction followed by a liquid chromatog. (LC)-mass spectrometry (MS)/high resolution mass spectrometry (HRMS) method for the simultaneous quantification of 19 NSAIDs in OF. After a comparison of different liquid-liquid extraction methods, a double step liquid-liquid extraction with chloroform was performed on OF collected with Quantisal, with extraction recoveries higher than 90%. An Accucore AQ column was selected for the chromatog. separation of NSAIDs. The Q Exactive Plus mass spectrometer operated in full scan and ddms2 mode after pos. and neg. electrospray ionization. Selectivity, carry-over, matrix effect, and linearity were validated for all NSAIDs. Within-day and between-day accuracy and precision were validated for all NSAIDs (<15% for quality control [QC] samples and <20% for lower limit of quantitation [LLOQ]), except within-day accuracy for the LLOQ of mefenamic acid. A stability study was also performed on OF at room temperature and +4°C. The method was applied on OF from runners who participate to Ultra Trail du Mont Blanc.

Drug Testing and Analysis published new progress about 169590-42-5. 169590-42-5 belongs to amides-buliding-blocks, auxiliary class Sulfamide,Immunology/Inflammation,COX, name is 4-(5-(p-Tolyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide, and the molecular formula is C17H14F3N3O2S, Application of 4-(5-(p-Tolyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide.

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

Boyle, Amanda J. published the artcileRepurposing [¹¹C]MC1 for PET Imaging of Cyclooxygenase-2 in Colorectal Cancer Xenograft Mouse Models, Quality Control of 169590-42-5, the publication is Molecular Imaging and Biology (2022), 24(3), 365-370, database is CAplus and MEDLINE.

Cyclooxygenase-2 (COX-2) is a target for inflammation and colorectal cancer (CRC). This study evaluated the COX-2 neuro-PET radiopharmaceutical, [¹¹C]MC1, in CRC xenograft mice. [¹¹C]MC1 was evaluated in ICRscid mice with HT-29 and HCT-116 CRC xenografts, with high and low COX-2 expression, resp., by immunohistochem., cellular uptake, dynamic PET/MR imaging, ex vivo biodistribution, and radiometabolite anal. HT-29 xenografts were well visualized with [¹¹C]MC1 using PET/MR. Time-activity curves revealed steady tumor radioactivity accumulation in HT-29 xenografts that plateaued from 40 to 60 min (3.07 ± 0.65 %ID/g) and was significantly reduced by pre-treatment with MC1 or celecoxib (1.62 ± 0.29 and 1.18 ± 0.21 %ID/g, resp., p = 0.045 and p = 0.005). Radiometabolite anal. showed that [¹¹C]MC1 accounted for >90 % of tumor radioactivity, with <10 % in plasma, at 40 min post-injection of the radiotracer. [¹¹C]MC1 is a promising PET imaging agent for COX-2 in CRC and translation for cancer research should be considered.

Molecular Imaging and Biology published new progress about 169590-42-5. 169590-42-5 belongs to amides-buliding-blocks, auxiliary class Sulfamide,Immunology/Inflammation,COX, name is 4-(5-(p-Tolyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide, and the molecular formula is C17H14F3N3O2S, Quality Control of 169590-42-5.

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

Kayser, Kevin published the artcileASD Formation Prior to Material Characterization as Key Parameter for Accurate Measurements and Subsequent Process Simulation for Hot-Melt Extrusion, Product Details of C17H14F3N3O2S, the publication is AAPS PharmSciTech (2022), 23(6), 176, database is CAplus and MEDLINE.

Process simulation facilitates scale-up of hot-melt extrusion (HME) and enhances proper understanding of the underlying critical process parameters. However, performing numeric simulations requires profound knowledge of the employed materials’ properties. For example, an accurate description of the compounds’ melt rheol. is paramount for proper simulations. Hence, sample preparation needs to be optimized to yield results as predictive as possible. To identify the optimal preparation method for small amplitude oscillatory shear (SAOS) rheol. measurements, binary mixtures of hydroxypropylmethylcellulose acetate succinate or methacrylic acid Et acrylate copolymer (Eudragit L100-55) together with the model drugs celecoxib and ketoconazole were prepared The phys. powder mixtures were introduced into the SAOS as a compressed tablet or a disk prepared via vacuum compression molding (VCM). Simulations with the derived parameters were conducted and compared to lab-scale extrusion trials. VCM was identified as the ideal preparation method resulting in the highest similarity between simulated and exptl. values, while simulation based on conventional powder-based methods insufficiently described the HME process.

AAPS PharmSciTech published new progress about 169590-42-5. 169590-42-5 belongs to amides-buliding-blocks, auxiliary class Sulfamide,Immunology/Inflammation,COX, name is 4-(5-(p-Tolyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide, and the molecular formula is C17H14F3N3O2S, Product Details of C17H14F3N3O2S.

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

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

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

Thompson, Patricia A published the artcileThe Importance of Drug Concentration at the Site of Action: Celecoxib and Colon Polyp Prevention as a Case Study., Product Details of C17H14F3N3O2S, the publication is Cancer prevention research (Philadelphia, Pa.) (2022), 15(4), 205-208, database is MEDLINE.

Celecoxib is among the more potent and better clinically studied, nonsteroidal anti-inflammatory drugs (NSAID) for use as a chemoprevention agent for colorectal cancer. Its use is associated with a 40% to 50% response rate for reduction in adenomatous polyps. However, rare serious cardiovascular effects and even death with celecoxib and other NSAIDs make it important to understand why some patients respond and others do not. Celecoxib is a selective inhibitor of COX-2. Its anticancer mechanism has largely been attributed to the inhibition of COX-2. Celecoxib also shows activity to induce apoptosis in cancer cells not expressing COX-2. This includes activity to upregulate 15-lipoxygenase-1 (15-LOX-1) independent of COX-2 and increase the synthesis of 13-S-hydroxyoctadecadienoic acid (13-S-HODE) from linoleic acid (LA) to downregulate PPAR-δ and induce apoptosis in colorectal cancer models. In examining the effect of celecoxib on 15-LOX-1 for reducing adenomatous polyps in patients with familial adenomatous polyposis (FAP), Yang and colleagues point out the potential importance of drug bioavailability in blood, normal, and neoplastic colorectal tissue in patient response. See related article, p. 217.

Cancer prevention research (Philadelphia, Pa.) published new progress about 169590-42-5. 169590-42-5 belongs to amides-buliding-blocks, auxiliary class Sulfamide,Immunology/Inflammation,COX, name is 4-(5-(p-Tolyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide, and the molecular formula is C4H6N2, Product Details of C17H14F3N3O2S.

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