Category: 71203-35-5

Caffo, Lindy published the artcileSimvastatin and ML141 Decrease Intracellular Streptococcus pyogenes Infection, Synthetic Route of 71203-35-5, the publication is Current Pharmaceutical Biotechnology (2019), 20(9), 733-744, database is CAplus and MEDLINE.

To determine whether simvastatin, a therapeutic approved for use in the treatment of hypercholesterolemia, and ML141, a first-in-class small mol. inhibitor with specificity for human CDC42, limit host cell invasion by S. pyogenes. Assays to assess host cell invasion, bactericidal activity, host cell viability, actin depolymerization, and fibronectin binding were performed using the RAW 267.4 macrophage cell line and Human Umbilical Vein Endothelial Cells (HUVEC) infected with S. pyogenes (90-226) and treated with simvastatin, ML141, structural analogs of ML141, or vehicle control. Simvastatin and ML141 decreased intracellular infection by S. pyogenes in a dose-dependent manner. Inhibition by simvastatin persisted following 1 h washout whereas inhibition by ML141 was reversed. During S. pyogenes infection, actin stress fibers depolymerized in vehicle control treated cells, yet remained intact in simvastatin and in ML141 treated cells. Consistent with the previous characterization of ML141, simvastatin decreased host cell binding to fibronectin. Structural analogs of ML141, designated as the RSM series, decreased intracellular infection through non-cytotoxic, nonbactericidal mechanisms. Our findings demonstrate the potential of repurposing simvastatin and of developing CDC42-targeted therapeutics for eradicating intracellular S. pyogenes infection to break the cycle of recurrent infection through a host-directed approach.

Current Pharmaceutical Biotechnology published new progress about 71203-35-5. 71203-35-5 belongs to pyrazoles-derivatives, auxiliary class GPCR/G Protein,Ras, name is 4-(5-(4-Methoxyphenyl)-3-phenyl-4,5-dihydro-1H-pyrazol-1-yl)benzenesulfonamide, and the molecular formula is C22H21N3O3S, Synthetic Route of 71203-35-5.

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

Xu, Jing published the artcileMolecular Mechanisms of the Blockage of Glioblastoma Motility, Name: 4-(5-(4-Methoxyphenyl)-3-phenyl-4,5-dihydro-1H-pyrazol-1-yl)benzenesulfonamide, the publication is Journal of Chemical Information and Modeling (2021), 61(6), 2967-2980, database is CAplus and MEDLINE.

Glioblastoma (GBM) is the most common and lethal brain tumor. GBM has a remarkable degree of motility and is able to infiltrate the healthy brain. In order to perform a rationale-based drug-repositioning study, we have used known inhibitors of two small Rho GTPases, Rac1 and Cdc42, which are upregulated in GBM and are involved in the signaling processes underlying the orchestration of the cytoskeleton and cellular motility. The selected inhibitors (R-ketorolac and ML141 for Cdc42 and R-ketorolac and EHT 1864 for Rac1) have been successfully employed to reduce the infiltration propensity of GBM in live cell imaging studies. Complementarily, all-atom simulations have elucidated the mol. basis of their inhibition mechanism, identifying the binding sites targeted by the inhibitors and dissecting their impact on the small Rho GTPases�function. Our results demonstrate the potential of targeting the Rac1 and Cdc42 proteins with small mols. to contrast GBM infiltration growth and supply precious information for future drug discovery studies aiming to fight GBM and other infiltrative cancer types.

Journal of Chemical Information and Modeling published new progress about 71203-35-5. 71203-35-5 belongs to pyrazoles-derivatives, auxiliary class GPCR/G Protein,Ras, name is 4-(5-(4-Methoxyphenyl)-3-phenyl-4,5-dihydro-1H-pyrazol-1-yl)benzenesulfonamide, and the molecular formula is C14H26O2, Name: 4-(5-(4-Methoxyphenyl)-3-phenyl-4,5-dihydro-1H-pyrazol-1-yl)benzenesulfonamide.

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

Thiruchelvi, R. published the artcileIn-Silico analysis to identify the potent inhibitor of Rho GTPase activating protein for the usage of the Glaucoma, SDS of cas: 71203-35-5, the publication is Materials Today: Proceedings (2021), 37(Part_2), 1897-1904, database is CAplus.

Considered as the one of the leading irreversible loss of vision causing optic neuropathy, Glaucoma is estimated to hit more than 80 million by the end of 2020 via population survey. Increased intraocular pressure is taken as one of the risk factors among others behind the root of causing the disease. The imbalance in the secretion and the excretion of the aqueous humor inside and out of the ocular results in the IOP to deviate from the normal value of 22 mm of Hg. The Rho GAP pathway playing a crucial role in the modulation of the contractile and relaxation property of the actin smooth muscle, has shown in neg. regulating the protein kinase and subsequently increased IOP. In-vitro and Ex-vitro inhibition of the Rho GTPase protein through inhibitors have resulted in the relaxation of the actin and hence the IOP. The aim of the study is to use the in-silico technique such as, Autodock4, to explore the ligand interaction and its ability to inhibit the activity of RhoGTPase. The mols. AZA1 and Azaindole, with the least binding energies, have proven to be a potent inhibitor of the protein, hence as a lead towards the treatment of the glaucoma by decreasing the IOP to an extent.

Materials Today: Proceedings published new progress about 71203-35-5. 71203-35-5 belongs to pyrazoles-derivatives, auxiliary class GPCR/G Protein,Ras, name is 4-(5-(4-Methoxyphenyl)-3-phenyl-4,5-dihydro-1H-pyrazol-1-yl)benzenesulfonamide, and the molecular formula is C20H23N3O2S, SDS of cas: 71203-35-5.

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

Mohapatra, Purusottam published the artcileCombination therapy targeting the elevated interleukin-6 level reduces invasive migration of BRAF inhibitor-resistant melanoma cells, Recommanded Product: 4-(5-(4-Methoxyphenyl)-3-phenyl-4,5-dihydro-1H-pyrazol-1-yl)benzenesulfonamide, the publication is Molecular Oncology (2019), 13(2), 480-494, database is CAplus and MEDLINE.

The identification of novel antimetastatic therapeutic targets is necessary for improved treatment of patients with acquired BRAF inhibitor-resistant (BRAFi-R) melanoma, in whom metastasis is a major concern. Our present study focused on the identification of such targets to explore novel antimetastatic therapeutic options for BRAFi-R melanoma patients. We confirmed the development of BRAFi resistance in our BRAFi-treated melanoma cell lines by demonstrating reduced sensitivity to BRAF inhibitors, increased ERK1/2 activity and increased WNT5A expression. Here, we demonstrated for the first time that high secretion of interleukin-6 (IL-6) was associated with increased invasive migration of BRAFi-R melanoma cells. This finding could be readily explained by the increased expression of WNT5A in BRAFi-R melanoma cells and the presence of an IL-6/WNT5A pos. feedback loop in parental melanoma cells. Surprisingly, however, we found that the IL-6/WNT5A pos. feedback loop present in parental melanoma cells was lost during the development of acquired BRAFi resistance, meaning that IL-6 and WNT5A signalling were independent events in BRAFi-R melanoma cells. Despite the absence of an IL-6/WNT5A loop, we found that both an IL-6 blocking antibody and the WNT5A antagonist Box5 alone impaired the elevated invasive migration of BRAFi-R melanoma cells, but combined use of the two was more effective. This impaired invasive migration of BRAFi-R melanoma cells correlated well with the reduction in Cdc42-GTPase activity and alterations of the actin cytoskeleton in these cells. In summary, our novel identification of IL-6 as a key independent promoter of the invasive migration of BRAFi-R melanoma cells stresses that a combination of a blocking IL-6 antibody and administration of the WNT5A antagonist Box5 might be an attractive antimetastatic approach for future treatment of BRAFi-R melanoma patients.

Molecular Oncology published new progress about 71203-35-5. 71203-35-5 belongs to pyrazoles-derivatives, auxiliary class GPCR/G Protein,Ras, name is 4-(5-(4-Methoxyphenyl)-3-phenyl-4,5-dihydro-1H-pyrazol-1-yl)benzenesulfonamide, and the molecular formula is C22H21N3O3S, Recommanded Product: 4-(5-(4-Methoxyphenyl)-3-phenyl-4,5-dihydro-1H-pyrazol-1-yl)benzenesulfonamide.

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

Feid-Allah, Hassan M. published the artcileTrisubstituted pyrazoles of possible antidiabetic and antibacterial activity, Related Products of pyrazoles-derivatives, the publication is Pharmazie (1981), 36(11), 754-6, database is CAplus.

Condensation of benzalacetone and dibenzalacetone with 4-H₂NSO₂C₆H₄NHNH₂ (I) and 2-pyridylhydrazine led to the corresponding hydrazones. These were readily cyclized to pyrazolines on heating with HCl. The reaction of substituted benzalacetophenones with I and 2-pyridylhydrazine gave the pyrazoline derivatives directly. Oxidation of the pyrazolines with Br-H₂O afforded the pyrazoles. Reaction of epoxy-p-methoxybenzalacetophenone with I gave a hydroxapyrazoline which oxidized to the hydroxypyrazole with Br-H₂O. Condensation of acylhydrazines with substituted benzalacetophenones afforded the corresponding acylhydrazones.

Pharmazie published new progress about 71203-35-5. 71203-35-5 belongs to pyrazoles-derivatives, auxiliary class GPCR/G Protein,Ras, name is 4-(5-(4-Methoxyphenyl)-3-phenyl-4,5-dihydro-1H-pyrazol-1-yl)benzenesulfonamide, and the molecular formula is C22H21N3O3S, Related Products of pyrazoles-derivatives.

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

Jayabal, Panneerselvam published the artcileNELL2-cdc42 signaling regulates BAF complexes and Ewing sarcoma cell growth, Synthetic Route of 71203-35-5, the publication is Cell Reports (2021), 36(1), 109254, database is CAplus and MEDLINE.

BAF chromatin remodeling complexes play important roles in chromatin regulation and cancer. Here, we report that Ewing sarcoma cells are dependent on the autocrine signaling mediated by NELL2, a secreted glycoprotein that has been characterized as an axon guidance mol. NELL2 uses Robo3 as the receptor to transmit critical growth signaling. NELL2 signaling inhibits cdc42 and upregulates BAF complexes and EWS-FLI1 transcriptional output. We demonstrate that cdc42 is a neg. regulator of BAF complexes, inducing actin polymerization and complex disassembly. Furthermore, we identify NELL2highCD133highEWS-FLI1 high and NELL2low CD133low EWS-FLI1low populations in Ewing sarcoma, which display phenotypes consistent with high and low NELL2 signaling, resp. We show that NELL2, CD133, and EWS-FLI1 pos. regulate each other and upregulate BAF complexes and cell proliferation in Ewing sarcoma. These results reveal a signaling pathway regulating critical chromatin remodeling complexes and cancer cell proliferation.

Cell Reports published new progress about 71203-35-5. 71203-35-5 belongs to pyrazoles-derivatives, auxiliary class GPCR/G Protein,Ras, name is 4-(5-(4-Methoxyphenyl)-3-phenyl-4,5-dihydro-1H-pyrazol-1-yl)benzenesulfonamide, and the molecular formula is C22H21N3O3S, Synthetic Route of 71203-35-5.

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

Che, Bingchen published the artcileDynamic intracellular mechanical cues facilitate collective signaling responses, SDS of cas: 71203-35-5, the publication is iScience (2021), 24(5), 102396, database is CAplus and MEDLINE.

Collective behavior emerges in diverse life machineries, e.g., the immune responses to dynamic stimulations. The essential questions that arise here are that whether and how cells in vivo collectively respond to stimulation frequencies higher than their intrinsic natural values, e.g., the acute inflammation conditions. In this work, we systematically studied morphol. and signaling responses of population fibroblasts in an interconnected cell monolayer and uncovered that, besides the natural NF-κB oscillation frequency of 1/90 min-1, collective signaling response emerges in the cell monolayer at 1/20 min-1 TNF-α input periodicity as well. Using a customized microfluidic device, we independently induced dynamic chem. stimulation and cytoskeleton reorganization on the stand-alone cells to exclude the effect of cell-cell communication. Our results reveal that, at this particular frequency, chem. stimulation is translated into dynamic intracellular mech. cues through RAC1-medicated induction of dynamic cell-cell connections and cytoskeleton reorganizations, which synergize with chem. input to facilitate collective signaling responses.

iScience published new progress about 71203-35-5. 71203-35-5 belongs to pyrazoles-derivatives, auxiliary class GPCR/G Protein,Ras, name is 4-(5-(4-Methoxyphenyl)-3-phenyl-4,5-dihydro-1H-pyrazol-1-yl)benzenesulfonamide, and the molecular formula is C22H21N3O3S, SDS of cas: 71203-35-5.

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

Zhang, Rong-Mo published the artcileThe fibrillin-1 RGD motif posttranscriptionally regulates ERK1/2 signaling and fibroblast proliferation via miR-1208, Application of 4-(5-(4-Methoxyphenyl)-3-phenyl-4,5-dihydro-1H-pyrazol-1-yl)benzenesulfonamide, the publication is FASEB Journal (2021), 35(5), e21598, database is CAplus and MEDLINE.

Fibrillin-1 is an extracellular matrix protein which contains one conserved RGD integrin-binding motif. It constitutes the backbone of microfibrils in many tissues, and mutations in fibrillin-1 cause various connective tissue disorders. Although it is well established that fibrillin-1 interacts with several RGD-dependent integrins, very little is known about the associated intracellular signaling pathways. Recent published evidence identified a subset of miRNAs regulated by fibrillin-1 RGD-cell adhesion, with miR-1208 among the most downregulated. The present study shows that the downregulated miR-1208 controls fibroblast proliferation. Inhibitor experiments revealed that fibrillin-1 RGD suppressed miR-1208 expression via c-Src kinase and the downstream JNK signaling. Bioinformatic prediction and exptl. target sequence validation demonstrated four miR-1208 binding sites on the ERK2 mRNA and one on the MEK1 mRNA. ERK2 and MEK1 are critical proliferation-promoting kinases. Decreased miR-1208 levels elevated the total and phosphorylated ERK1/2 and MEK1/2 protein levels and the phosphorylated to total ERK1/2 ratio. Together, the data demonstrate a novel outside-in signaling mechanism explaining how fibrillin-1 RGD-cell binding regulates fibroblast proliferation.

FASEB Journal published new progress about 71203-35-5. 71203-35-5 belongs to pyrazoles-derivatives, auxiliary class GPCR/G Protein,Ras, name is 4-(5-(4-Methoxyphenyl)-3-phenyl-4,5-dihydro-1H-pyrazol-1-yl)benzenesulfonamide, and the molecular formula is C15H20N2O2, Application of 4-(5-(4-Methoxyphenyl)-3-phenyl-4,5-dihydro-1H-pyrazol-1-yl)benzenesulfonamide.

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

Valsalakumari, Remya published the artcileMechanism of cellular uptake and cytotoxicity of paclitaxel loaded lipid nanocapsules in breast cancer cells, Recommanded Product: 4-(5-(4-Methoxyphenyl)-3-phenyl-4,5-dihydro-1H-pyrazol-1-yl)benzenesulfonamide, the publication is International Journal of Pharmaceutics (Amsterdam, Netherlands) (2021), 120217, database is CAplus and MEDLINE.

Lipid nanocapsules (LNCs) have proven their efficacy in delivering different drugs to various cancers, but no studies have yet described their uptake mechanisms, paclitaxel (PTX) delivery or resulting cytotoxicity towards breast cancer cells. Herein, we report results concerning cellular uptake of LNCs and cytotoxicity studies of PTX-loaded LNCs (LNCs-PTX) on the three breast cancer cell lines MCF-7, MDA-MB-231 and MDA-MB-468. LNCs-PTX of sizes 50 ± 2 nm, 90 ± 3 nm and 120 ± 4 nm were developed by the phase inversion method. Fluorescence microscopy and flow cytometry were used to observe the uptake of fluorescently labeled LNCs and cellular uptake of LNCs-PTX was measured using HPLC analyses of cell samples. These studies revealed a higher uptake of LNCs-PTX in MDA-MB-468 cells than in the other two cell lines. Moreover, free PTX and LNCs-PTX exhibited a similar pattern of toxicity towards each cell line, but MDA-MB-468 cells appeared to be more sensitive than the other two cell lines, as evaluated by the MTT cytotoxicity assay and a cell proliferation assay based upon [3H]thymidine incorporation. Studies with inhibitors of endocytosis indicate that the cellular uptake is mainly via the Cdc42/GRAF-dependent endocytosis as well as by macropinocytosis, whereas dynamin-dependent processes are not required. Furthermore, our results indicate that endocytosis of LNCs-PTX is important for the toxic effect on cells. Western blot anal. revealed that LNCs-PTX induce cytotoxicity by means of apoptosis in all the three cell lines. Altogether, the results demonstrate that LNCs-PTX exploit different mechanisms of endocytosis in a cell-type dependent manner, and subsequently induce apoptotic cell death in the breast cancer cells here studied. The article also describes biodistribution studies following i.v. injection of fluorescently labeled LNCs in mice.

International Journal of Pharmaceutics (Amsterdam, Netherlands) published new progress about 71203-35-5. 71203-35-5 belongs to pyrazoles-derivatives, auxiliary class GPCR/G Protein,Ras, name is 4-(5-(4-Methoxyphenyl)-3-phenyl-4,5-dihydro-1H-pyrazol-1-yl)benzenesulfonamide, and the molecular formula is C12H9N3O4, Recommanded Product: 4-(5-(4-Methoxyphenyl)-3-phenyl-4,5-dihydro-1H-pyrazol-1-yl)benzenesulfonamide.

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

Popkova, Anna published the artcileA Cdc42-mediated supracellular network drives polarized forces and Drosophila egg chamber extension, Application of 4-(5-(4-Methoxyphenyl)-3-phenyl-4,5-dihydro-1H-pyrazol-1-yl)benzenesulfonamide, the publication is Nature Communications (2020), 11(1), 1921, database is CAplus and MEDLINE.

Abstract: Actomyosin supracellular networks emerge during development and tissue repair. These cytoskeletal structures are able to generate large scale forces that can extensively remodel epithelia driving tissue buckling, closure and extension. How supracellular networks emerge, are controlled and mech. work still remain elusive. During Drosophila oogenesis, the egg chamber elongates along the anterior-posterior axis. Here we show that a dorsal-ventral polarized supracellular F-actin network, running around the egg chamber on the basal side of follicle cells, emerges from polarized intercellular filopodia that radiate from basal stress fibers and extend penetrating neighboring cell cortexes. Filopodia can be mechanosensitive and function as cell-cell anchoring sites. The small GTPase Cdc42 governs the formation and distribution of intercellular filopodia and stress fibers in follicle cells. Finally, our study shows that a Cdc42-dependent supracellular cytoskeletal network provides a scaffold integrating local oscillatory actomyosin contractions at the tissue scale to drive global polarized forces and tissue elongation.

Nature Communications published new progress about 71203-35-5. 71203-35-5 belongs to pyrazoles-derivatives, auxiliary class GPCR/G Protein,Ras, name is 4-(5-(4-Methoxyphenyl)-3-phenyl-4,5-dihydro-1H-pyrazol-1-yl)benzenesulfonamide, and the molecular formula is C22H21N3O3S, Application of 4-(5-(4-Methoxyphenyl)-3-phenyl-4,5-dihydro-1H-pyrazol-1-yl)benzenesulfonamide.

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