Tag: M.W=350-400

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

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

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

Guo, Wei published the artcileImrecoxib versus celecoxib as postoperative analgesia for patients receiving arthroscopic knee surgery: a randomized, controlled, non-inferiority study, HPLC of Formula: 169590-42-5, the publication is Inflammopharmacology (2022), 30(3), 875-881, database is CAplus and MEDLINE.

Objective: Imrecoxib is a novel cyclooxygenase-2 inhibitor independently developed in China, which exhibits a good efficacy and tolerance in orthopedic disorders. The current study aimed to further compare its efficacy and safety with celecoxib as postoperative analgesia in arthroscopic knee surgery (AKS). Methods: Patients receiving AKS were enrolled and randomly assigned to imrecoxib (n = 64) and celecoxib (n = 62) group to receive analgesia for 72 h after surgery. Pain at rest and movement, pethidine consumption, patient′s satisfaction, Lysholm score, and adverse events were assessed after AKS. Meanwhile the upper limit of 95CI of pain-score mean difference (MD) between imrecoxib and celecoxib was calculated, then, the non-inferiority was defined if the all-time-point upper limits of 95CI less than 1. Results: Imrecoxib was non-inferior to celecoxib for alleviating pain at rest (upper limit of 95CI of MD ranging from 0.443 to 0.782, all time-point values less than 1); as well as for attenuating pain at movement (upper limit of 95CI of MD ranging from 0.398 to 0.582, all time-point values less than 1). Moreover, rescue analgesia rate (P = 0.583), pethidine consumption (P = 0.454), patient′s satisfaction at 72 h (P = 0.408), and Lysholm score at M3 (P = 0.776) were of no difference between imrecoxib group and celecoxib group. Addnl., the main adverse events in two groups were nausea (P = 0.425), constipation (P = 1.000), vomiting (P = 0.715), headache (P = 1.000), and dizziness (P = 0.667), which were mild and manageable. Conclusion: Imrecoxib is non-inferior to celecoxib in postoperative analgesia and exhibits an acceptable tolerance in patients undergoing AKS.

Inflammopharmacology 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, HPLC of Formula: 169590-42-5.

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

Shi, Zhaojiang published the artcileElectrochemical Migratory Cyclization of N-Acylsulfonamides, HPLC of Formula: 169590-42-5, the publication is Angewandte Chemie, International Edition (2022), 61(30), e202206058, database is CAplus and MEDLINE.

Herein a facile electrochem. migratory cyclization of N-acylsulfonamides was reported to access a diverse array of benzoxathiazine dioxides I [R = H, 2-OMe, 4-F, etc.; R¹ = H, Ph, 2-pyridyl, etc.]. The inclusion of electrochem. was crucial for realizing such a novel transformation, which is substantiated both by the experiments and d.-functional-theory calculations

Angewandte Chemie, International Edition 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 C7H16ClNO2, HPLC of Formula: 169590-42-5.

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

Zhang, Tian-Yi published the artcileNew ursolic acid derivatives bearing 1,2,3-triazole moieties: design, synthesis and anti-inflammatory activity in vitro and in vivo, Formula: C17H14F3N3O2S, the publication is Molecular Diversity (2022), 26(2), 1129-1139, database is CAplus and MEDLINE.

In order to discover novel anti-inflammatory agents, three series of compounds obtained by appending 1,2,3-triazole moieties on ursolic acid I [n = 3; R¹ = H, 2-F, 4-Me, 3,4-(CH₃)₂], II [R² = H, 3-OMe, 2,4-(CH₃)₂, 3-CF₃, 2,4-Cl₂; X = O, NH], III (R³ = Ph, 2,3-dimethoxyphenyl, furan-2-yl, etc.) were designed and synthesized. All compounds have been screened for their anti-inflammatory activity by using an ear edema model. The potent anti-inflammatory compound was subjected to in vitro cyclooxygenase COX-1/COX-2 inhibition assays. In general, the derivatives were found to be potent anti-inflammatory activity. Especially, the compound I (n = 3; R³ = 2,3-dimethoxyphenyl) (IV) exhibited the strongest activity of all of the compounds prepared, with 82.81% inhibition after i.p. administration, which was better than celecoxib as a pos. control. Mol. docking results unclose the rationale for the interaction of the compound IV with COX-2 enzyme. Further studies revealed that compound IV exhibited effective COX-2 inhibitory activity, with half-maximal inhibitor concentration (IC₅₀) value of 1.16μM and selectivity index (SI = 64.66) value close to that of celecoxib (IC₅₀ = 0.93μM, SI = 65.47). Taken together, these results could suggest a promising chemotype for development of new COX-2-targeting anti-inflammatory agent.

Molecular Diversity 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 C10H11NO4, Formula: C17H14F3N3O2S.

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

Wu, Ziying published the artcileAssociation between tramadol use and risk of pneumonia in the middle-aged and elderly populations: a propensity-score matched cohort study, SDS of cas: 169590-42-5, the publication is European Journal of Pain (Oxford, United Kingdom) (2022), 26(6), 1245-1255, database is CAplus and MEDLINE.

Tramadol is a widely used weak opioid; however, the evidence for its safety profile in respiratory system needs addnl. information. We aimed to examine whether tramadol use is associated with an increased risk of pneumonia in the general population. We conducted five propensity-score (PS) matched cohort studies in The Health Improvement Network database. Participants aged ≥50-years initiated tramadol were compared with those initiated one of the following analgesics: codeine (n = 144,506), naproxen (n = 113,028), diclofenac (n = 74,297), celecoxib (n = 42,538), or etoricoxib (n = 27,232). The outcome was incident pneumonia. During 6-mo follow-up, 395 pneumonia (5.6/1000 person-years) occurred in the tramadol group and 414 pneumonia (5.9/1000 person-years) occurred in the PS matched codeine group. Compared with codeine group, the risk of pneumonia was lower in the tramadol group (hazard ratio [HR] = 0.63, 95% confidence interval [CI]: 0.49-0.82) during the first 30-day follow-up, but comparable between groups over the entire 6-mo follow-up (HR = 0.95, 95%CI: 0.83-1.09). In addition, the risk of pneumonia was higher in the tramadol group than that in the PS matched naproxen (HR = 1.68, 95%CI: 1.37-2.06), diclofenac (HR = 1.63, 95%CI: 1.31-2.03), celecoxib (HR = 1.64, 95%CI: 1.20-2.24) or etoricoxib (HR = 1.61, 95%CI: 1.04-2.49) group. The present study indicated that tramadol initiators had a lower risk of incident pneumonia than codeine initiators during the short-time follow-up, but had a comparable pneumonia risk compared with codeine initiators and had a higher risk of pneumonia compared with NSAIDs initiators over the entire 6-mo follow-up duration. Confirmation of the present findings and determination of the underlying mechanism will require more studies. Tramadol might not be a safer alternative analgesic to codeine or NSAIDs. Both of health-care providers and patients may need to be on alert for its safety profile in respiratory system in future clin. practice.

European Journal of Pain (Oxford, 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 C4H11NO, SDS of cas: 169590-42-5.

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

Rao, Chinthalapally V. published the artcileAnti-inflammatory Drugs Decrease the PD-L1 Expression and Increase the CD8⁺ T-Cell Infiltration, Synthetic Route of 169590-42-5, the publication is Cancer Prevention Research (2022), 15(4), 209-211, database is CAplus and MEDLINE.

In this issue of Cancer Prevention Research, Cecil and colleagues show that nonsteroidal anti-inflammatory drugs (NSAID), celecoxib and naproxen, decrease the expression of programmed death-ligand 1 (PD-L1) and increase the influx of Type I tumor-infiltrating lymphocytes in colonic tumors. Importantly, both decrease of PD-L1 expression and increase of CD8+ T cells were associated with the inhibition of COX-2/PGE2 pathway in vitro and syngeneic colonic tumor xenograft models. This study clearly suggests that NSAIDs regulate the intratumoral immunity multiple ways, including suppression of expression of immune checkpoint blockade. Thus, NSAIDs should be considered as chemopreventive for patients with PD-L1-pos. colonic polyp.

Cancer Prevention 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, Synthetic Route of 169590-42-5.

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