Category: 169590-42-5

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

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

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

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

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

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

Orr, Brian published the artcilePhase I trial combining chemokine-targeting with loco-regional chemoimmunotherapy for recurrent, platinum-sensitive ovarian cancer shows induction of CXCR3 ligands and markers of type 1 immunity, Application of 4-(5-(p-Tolyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide, the publication is Clinical Cancer Research (2022), 28(10), 2038-2049, database is CAplus and MEDLINE.

Increased prevalence of cytotoxic T lymphocytes (CTL) in the tumor microenvironment (TME) predicts pos. outcomes in patients with epithelial ovarian cancer (EOC), whereas the regulatory T cells (Treg) predict poor outcomes. Guided by the synergistic activity of TLR3 ligands, IFNα, and COX-2 blockers in selectively enhancing CTL-attractants but suppressing Treg-attractants, we tested a novel i.p. chemoimmunotherapy combination (CITC), to assess its tolerability and TME-modulatory impact in patients with recurrent EOC. Twelve patients were enrolled in phase I portion of the trial NCT02432378, and treated with i.p. cisplatin, i.p. rintatolimod (dsRNA, TLR3 ligand), and oral celecoxib (COX-2 blocker). Patients in cohorts 2, 3, and 4 also received i.p. IFNα at 2, 6, and 18 million units (MU), resp. Primary objectives were to evaluate safety, identify phase 2 recommended dose (P2RD), and characterize changes in the immune TME. Peritoneal resident cells and i.p. wash fluid were profiled via NanoString and Meso Scale Discovery (MSD) multiplex assay, resp. The P2RD of IFNα was 6 MU. Median progression-free survival and overall survival were 8.4 and 30 mo, resp. Longitudinal sampling of the peritoneal cavity via i.p. washes demonstrated local upregulation of IFN-stimulated genes (ISG), including CTL-attracting chemokines (CXCL-9, -10, -11), MHC I/II, perforin, and granzymes. These changes were present 2 days after chemokine modulation and subsided within 1 wk. The chemokine-modulating i.p.-CITC is safe, tolerable, and associated with ISG changes that favor CTL chemoattraction and function. This combination (plus DC vaccine) will be tested in a phase II trial.

Clinical Cancer Research 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

Zhang, Cong published the artcileCelecoxib attenuates hepatosteatosis by impairing de novo lipogenesis via Akt-dependent lipogenic pathway., Computed Properties of 169590-42-5, the publication is Journal of cellular and molecular medicine (2022), 26(14), 3995-4006, database is MEDLINE.

Mounting evidence indicates that hepatic de novo lipogenesis is a common abnormality in non-alcoholic fatty liver disease (NAFLD) patients. We investigated whether a selective COX-2 inhibitor, celecoxib, alleviates hepatic steatosis by targeting an Akt-driven lipogenic pathway. We estimated the efficacy of celecoxib in a novel Akt-driven NAFLD mouse model established via hydrodynamic transfection of activated forms of AKT and in fructose-fed NAFLD mice that exhibited increased insulin-independent hepatic lipogenesis. AKT-transfected and insulin-stimulated human hepatoma cells were used for the in vitro experiments. Haematoxylin and eosin staining, immunohistochemistry and immunoblotting were performed for mechanistic studies. The results revealed that celecoxib ameliorated hepatic steatosis in the AKT-triggered NAFLD mice. Mechanistically, celecoxib effectively suppressed AKT/mTORC1 signalling and its downstream lipogenic cascade in the Akt-driven NAFLD mice and in vitro. Furthermore, celecoxib had limited efficacy in alleviating hepatic lipid accumulation and showed no influence on lipogenic proteins associated with hepatic lipogenesis in fructose-administered mice. This study suggests that celecoxib may be favourable for the treatment of NAFLD, especially in the subset with Akt-triggered hepatic lipogenesis.

Journal of cellular and molecular medicine 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 C7H7ClN2S, Computed Properties of 169590-42-5.

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

Urbina, Fabio published the artcileMegaSyn: Integrating Generative Molecular Design, Automated Analog Designer, and Synthetic Viability Prediction, Application of 4-(5-(p-Tolyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide, the publication is ACS Omega (2022), 7(22), 18699-18713, database is CAplus and MEDLINE.

Generative machine learning models have become widely adopted in drug discovery and other fields to produce new mols. and explore mol. space, with the goal of discovering novel compounds with optimized properties. These generative models are frequently combined with transfer learning or scoring of the physicochem. properties to steer generative design, yet often, they are not capable of addressing a wide variety of potential problems, as well as converge into similar mol. space when combined with a scoring function for the desired properties. In addition, these generated compounds may not be synthetically feasible, reducing their capabilities and limiting their usefulness in real-world scenarios. Here, we introduce a suite of automated tools called MegaSyn representing three components: a new hill-climb algorithm, which makes use of SMILES-based recurrent neural network (RNN) generative models, analog generation software, and retrosynthetic anal. coupled with fragment anal. to score mols. for their synthetic feasibility. We show that by deconstructing the targeted mols. and focusing on substructures, combined with an ensemble of generative models, MegaSyn generally performs well for the specific tasks of generating new scaffolds as well as targeted analogs, which are likely synthesizable and druglike. We now describe the development, benchmarking, and testing of this suite of tools and propose how they might be used to optimize mols. or prioritize promising lead compounds using these RNN examples provided by multiple test case examples.

ACS Omega 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 C15H12O6, 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

Tsai, Yu-Ting published the artcileReprogramming of arachidonate metabolism confers temozolomide resistance to glioblastoma through enhancing mitochondrial activity in fatty acid oxidation, Product Details of C17H14F3N3O2S, the publication is Journal of Biomedical Science (London, United Kingdom) (2022), 29(1), 21, database is CAplus and MEDLINE.

Sp1 is involved in the recurrence of glioblastoma (GBM) due to the acquirement of resistance to temozolomide (TMZ). Particularly, the role of Sp1 in metabolic reprogramming for drug resistance remains unknown. RNA-Seq and mass spectrometry were used to analyze gene expression and metabolites amounts in paired GBM specimens (primary vs. recurrent) and in paired GBM cells (sensitive vs. resistant). ω-3/6 fatty acid and arachidonic acid (AA) metabolism in GBM patients were analyzed by targeted metabolome. Mitochondrial functions were determined by Seahorse XF Mito Stress Test, RNA-Seq, metabolome and substrate utilization for producing ATP. Therapeutic options targeting prostaglandin (PG) E2 in TMZ-resistant GBM were validated in vitro and in vivo. Among the metabolic pathways, Sp1 increased the prostaglandin-endoperoxide synthase 2 expression and PGE2 production in TMZ-resistant GBM. Mitochondrial genes and metabolites were obviously increased by PGE2, and these characteristics were required for developing resistance in GBM cells. For inducing TMZ resistance, PGE2 activated mitochondrial functions, including fatty acid β-oxidation (FAO) and tricarboxylic acid (TCA) cycle progression, through PGE2 receptors, E-type prostanoid (EP)1 and EP3. Addnl., EP1 antagonist ONO-8713 inhibited the survival of TMZ-resistant GBM synergistically with TMZ. Sp1-regulated PGE2 production activates FAO and TCA cycle in mitochondria, through EP1 and EP3 receptors, resulting in TMZ resistance in GBM. These results will provide us a new strategy to attenuate drug resistance or to re-sensitize recurred GBM.

Journal of Biomedical Science (London, United Kingdom) 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 C13H10O3, Product Details of C17H14F3N3O2S.

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