M.W=400-450 | Page 3 of 4 | pyrazoles-derivatives

Thottacherry, Joseph Jose’s team published research in Nature Communications in 9 | CAS: 71203-35-5

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 C20H19NO4, HPLC of Formula: 71203-35-5.

Thottacherry, Joseph Jose published the artcileMechanochemical feedback control of dynamin independent endocytosis modulates membrane tension in adherent cells, HPLC of Formula: 71203-35-5, the publication is Nature Communications (2018), 9(1), 1-14, database is CAplus and MEDLINE.

Plasma membrane tension regulates many key cellular processes. It is modulated by, and can modulate, membrane trafficking. However, the cellular pathway(s) involved in this interplay is poorly understood. Here we find that, among a number of endocytic processes operating simultaneously at the cell surface, a dynamin independent pathway, the CLIC/GEEC (CG) pathway, is rapidly and specifically upregulated upon a sudden reduction of tension. Moreover, inhibition (activation) of the CG pathway results in lower (higher) membrane tension. However, alteration in membrane tension does not directly modulate CG endocytosis. This requires vinculin, a mechano-transducer recruited to focal adhesion in adherent cells. Vinculin acts by controlling the levels of a key regulator of the CG pathway, GBF1, at the plasma membrane. Thus, the CG pathway directly regulates membrane tension and is in turn controlled via a mechano-chem. feedback inhibition, potentially leading to homeostatic regulation of membrane tension in adherent cells.

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

Hong, Lin’s team published research in Journal of Biological Chemistry in 288 | CAS: 71203-35-5

Journal of Biological Chemistry 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, COA of Formula: C22H21N3O3S.

Hong, Lin published the artcileCharacterization of a Cdc42 Protein Inhibitor and Its Use as a Molecular Probe, COA of Formula: C22H21N3O3S, the publication is Journal of Biological Chemistry (2013), 288(12), 8531-8543, database is CAplus and MEDLINE.

Cdc42 plays important roles in cytoskeleton organization, cell cycle progression, signal transduction, and vesicle trafficking. Overactive Cdc42 has been implicated in the pathol. of cancers, immune diseases, and neuronal disorders. Therefore, Cdc42 inhibitors would be useful in probing mol. pathways and could have therapeutic potential. Previous inhibitors have lacked selectivity and trended toward toxicity. We report here the characterization of a Cdc42-selective guanine nucleotide binding lead inhibitor that was identified by high throughput screening. A second active analog was identified via structure-activity relationship studies. The compounds demonstrated excellent selectivity with no inhibition toward Rho and Rac in the same GTPase family. Biochem. characterization showed that the compounds act as noncompetitive allosteric inhibitors. When tested in cellular assays, the lead compound inhibited Cdc42-related filopodia formation and cell migration. The lead compound was also used to clarify the involvement of Cdc42 in the Sin Nombre virus internalization and the signaling pathway of integrin VLA-4. Together, these data present the characterization of a novel Cdc42-selective allosteric inhibitor and a related analog, the use of which will facilitate drug development targeting Cdc42-related diseases and mol. pathway studies that involve GTPases.

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

Liu, Lingling’s team published research in Biochemical and Biophysical Research Communications in 519 | CAS: 71203-35-5

Biochemical and Biophysical Research 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, HPLC of Formula: 71203-35-5.

Liu, Lingling published the artcileCdc42-mediated supracellular cytoskeleton induced cancer cell migration under low shear stress, HPLC of Formula: 71203-35-5, the publication is Biochemical and Biophysical Research Communications (2019), 519(1), 134-140, database is CAplus and MEDLINE.

Tumor microenvironment is composed of biol., chem. and phys. factors. Mech. factors are more and more focused these years. Therefore, mimicking mech. factors’ contribution to cancer cell malignancy will greatly improve the advance in this field. Although the induced malignant behaviors are present under many stimuli such as growth or inflammatory factors, the cell key phys. migration mechanisms are still missing. In this study, we identify that low shear stress significantly promotes the formation of needle-shaped membrane protrusions, which is called filopodia and important for the sense and interact of a cell with extracellular matrix in the tumor microenvironment. Under low shear stress, the migration is promoted while it is inhibited in the presence of ROCK inhibitor Y27632, which could abolish the F-actin network. Using cell imaging, we further unravel that key to these protrusions is Cell division cycle 42 (Cdc42) dependent. After Cdc42 activation, the filopodia is more and longer, acting as massagers to pass the information from a cell to the microenvironment for its malignant phenotype. In the Cdc42 inhibition, the filopodia is greatly reduced. Moreover, small GTPases Cdc42 rather than Rac1 and Rho directly controls the filopodia formation. Our work highlights that low shear stress and Cdc42 activation are sufficient to promote filopodia formation, it not only points out the novel structure for cancer progression but also provides the exptl. phys. basis for the efficient drug anti-cancer strategies.

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

Hanna, Samer J.’s team published research in Scientific Reports in 7 | CAS: 71203-35-5

Scientific 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, Recommanded Product: 4-(5-(4-Methoxyphenyl)-3-phenyl-4,5-dihydro-1H-pyrazol-1-yl)benzenesulfonamide.

Hanna, Samer J. published the artcileThe Role of Rho-GTPases and actin polymerization during Macrophage Tunneling Nanotube Biogenesis, Recommanded Product: 4-(5-(4-Methoxyphenyl)-3-phenyl-4,5-dihydro-1H-pyrazol-1-yl)benzenesulfonamide, the publication is Scientific Reports (2017), 7(1), 1-16, database is CAplus and MEDLINE.

Macrophage interactions with other cells, either locally or at distances, are imperative in both normal and pathol. conditions. While soluble means of communication can transmit signals between different cells, it does not account for all long distance macrophage interactions. Recently described tunneling nanotubes (TNTs) are membranous channels that connect cells together and allow for transfer of signals, vesicles, and organelles. However, very little is known about the mechanism by which these structures are formed. Here we investigated the signaling pathways involved in TNT formation by macrophages using multiple imaging techniques including super-resolution microscopy (3D-SIM) and live-cell imaging including the use of FRET-based Rho GTPase biosensors. We found that formation of TNTs required the activity and differential localization of Cdc42 and Rac1. The downstream Rho GTPase effectors mediating actin polymerization through Arp2/3 nucleation, Wiskott-Aldrich syndrome protein (WASP) and WASP family verprolin-homologous 2 (WAVE2) proteins are also important, and both pathways act together during TNT biogenesis. Finally, TNT function as measured by transfer of cellular material between cells was reduced following depletion of a single factor demonstrating the importance of these factors in TNTs. Given that the characterization of TNT formation is still unclear in the field; this study provides new insights and would enhance the understanding of TNT formation towards investigating new markers.

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

Wirth, Franziska’s team published research in Bone (New York, NY, United States) in 153 | CAS: 71203-35-5

Bone (New York, NY, United States) 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 C10H10O2, Application of 4-(5-(4-Methoxyphenyl)-3-phenyl-4,5-dihydro-1H-pyrazol-1-yl)benzenesulfonamide.

Wirth, Franziska published the artcileCdc42 in osterix-expressing cells alters osteoblast behavior and myeloid lineage commitment, Application of 4-(5-(4-Methoxyphenyl)-3-phenyl-4,5-dihydro-1H-pyrazol-1-yl)benzenesulfonamide, the publication is Bone (New York, NY, United States) (2021), 116150, database is CAplus and MEDLINE.

Osteoblasts are not only responsible for bone formation. They also support hematopoiesis. This requires responding to cues originating from several signaling pathways, a task performed by Rho GTPases. We therefore examined several transgenic mouse models and used inhibitors of Cdc42 in vitro. Deletion of Cdc42 in vivo using the Osterix promoter suppressed osteoblast function, while its deletion in differentiating osteoblasts using the Collagen-伪1(I) promoter decreased osteoblast numbers In both cases, bone mineral d. diminished confirming the importance of Cdc42. Evaluation of hematopoiesis revealed that deletion of Cdc42 using the Osterix, but not the Collagen-伪1(I) promoter increased the common myeloid progenitors (CMPs) in the bone marrow as well as the erythrocytes and the thrombocytes/platelets in peripheral blood. Causality between Cdc42 loss in early osteoblasts and increased myelopoiesis was confirmed in vitro. Work in vitro supported the conclusion that interleukin-4 mediated the increase in myelopoiesis. Thus, Cdc42 is required for healthy bone through regulation of bone formation in Osterix-expressing osteoblasts and the number of osteoblasts in differentiating osteoblasts. In addition, its expression in early osteoblasts/stromal cells modulates myelopoiesis. This highlights the importance of osteoblasts in regulating hematopoiesis.

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

Zheng, Yan-qiu’s team published research in Xiandai Shengwuyixue Jinzhan in 16 | CAS: 71203-35-5

Xiandai Shengwuyixue Jinzhan 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 C16H24BF4Ir, Related Products of pyrazoles-derivatives.

Zheng, Yan-qiu published the artcileCDC42 inhibitor ML141 suppresses laryngeal cancer Hep-2 cell proliferation, Related Products of pyrazoles-derivatives, the publication is Xiandai Shengwuyixue Jinzhan (2016), 16(4), 644-646, 651, database is CAplus.

Objective: Investigating the effect of CDC42 inhibitor ML141 on Hep-2 cell proliferation to provide new targets for mol. therapy of laryngeal cancer. Methods: Hep-2 cells were cultured in vitro. Real-time PCR was used to identify the expression of CDC42 in Hep-2 cell. GLISA was carried out to detect the changes in activation of CDC42 in Hep-2 cell treated with ML141. CCK8 assay was used to detect the effect of ML141 on Hep-2 cell proliferation. Results: 1. The result of Real-time PCR showed that CDC42 gene was differentially expressed in Hep-2 cells, which was consistent with the results of the whole genome profiling (P < 0.001). 2. The result of GLISA showed that epidermal growth factor (EGF) could increase the activation of CDC42 in Hep-2 cell but ML141 could inhibit its activation significantly (p < 0.001). 3. The result of CCK8 showed that the proliferation of Hep-2 cell was significantly inhibited by treating with ML141 after 24 h, 48 h and 72 h compared with control group (P < 0.001). Conclusion: CDC42 inhibitor ML141 could inhibit the proliferation of Hep-2 cell. ML141 might have the potential to become the new anti-cancer drug, which provided a new target point for mol. therapy of laryngeal cancer.

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

Guha, Rajarshi’s team published research in Journal of Biomolecular Screening in 21 | CAS: 71203-35-5

Journal of Biomolecular Screening 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, Category: pyrazoles-derivatives.

Guha, Rajarshi published the artcileRanking differential drug activities from dose-response synthetic lethality screens, Category: pyrazoles-derivatives, the publication is Journal of Biomolecular Screening (2016), 21(9), 942-955, database is CAplus and MEDLINE.

Synthetic lethal screens are used to discover new combination treatments for cancer. In traditional high-throughput synthetic lethal screens, compounds are tested at a single dose, and hit selection is based on threshold activity values from the variance of the efficacy of the compounds tested. The limitation of the single-dose screening for synthetic lethal screens is that it does not allow for the robust detection of differential activities from compound collections with a broad range of potencies and efficacies. There is therefore a need to develop screening approaches that enable the identification of compounds with synthetic lethal effects based on changes in both potency and efficacy. Here we describe the implementation of a dose response-based synthetic lethal screen to find drugs that enhance or mitigate the cytotoxic effect of an immunotoxin protein (HA22). We developed a data anal. framework for the selection of compounds with enhancing or mitigating cytotoxic activities based on the use of dose-response parameters. The data anal. framework includes an ensemble ranking approach that allows the use of multiple dose-response parameters in a nonparametric fashion. Quant. high-throughput screening (HTS) enables the identification of compounds with synthetic lethal activity not identified by single-dose HTS.

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

Nguyen, Duc-Huy T.’s team published research in Microcirculation (Oxford, United Kingdom) in 24 | CAS: 71203-35-5

Microcirculation (Oxford, United Kingdom) 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.

Nguyen, Duc-Huy T. published the artcileCdc42 regulates branching in angiogenic sprouting in vitro, Recommanded Product: 4-(5-(4-Methoxyphenyl)-3-phenyl-4,5-dihydro-1H-pyrazol-1-yl)benzenesulfonamide, the publication is Microcirculation (Oxford, United Kingdom) (2017), 24(5), n/a, database is CAplus and MEDLINE.

The morphogenetic events that occur during angiogenic sprouting involve several members of the Rho family of GTPases, including Cdc42. However, the precise roles of Cdc42 in angiogenic sprouting have been difficult to elucidate owing to the lack of models to study these events in vitro. Here, we aim to identify the roles of Cdc42 in branching morphogenesis in angiogenesis. Using a 3D biomimetic model of angiogenesis in vitro, where endothelial cells were seeded inside a cylindrical channel within collagen gel and sprouted from the channel in response to a defined biochem. gradient of angiogenic factors, we inhibited Cdc42 activity with a small mol. inhibitor ML141 and examined the effects of Cdc42 on the morphogenetic processes of angiogenic sprouting. We find that partial inhibition of Cdc42 had minimal effects on directional migration of endothelial cells, but led to fewer branching events without affecting the length of these branches. We also observed that antagonizing Cdc42 reduced collective migration in favor of single cell migration. Addnl., Cdc42 also regulated the initiation of filopodial extensions in endothelial tip cells. Our findings suggest that Cdc42 can affect multiple morphogenetic processes during angiogenic sprouting and ultimately impact the architecture of the vasculature.

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

Lucera, Mark B.’s team published research in Retrovirology in 14 | CAS: 71203-35-5

Retrovirology 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, HPLC of Formula: 71203-35-5.

Lucera, Mark B. published the artcileHIV signaling through CD4 and CCR5 activates Rho family GTPases that are required for optimal infection of primary CD4+ T cells, HPLC of Formula: 71203-35-5, the publication is Retrovirology (2017), 4/1-4/13, database is CAplus and MEDLINE.

Background: HIV-1 hijacks host cell machinery to ensure successful replication, including cytoskeletal components for intracellular trafficking, nucleoproteins for pre-integration complex import, and the ESCRT pathway for assembly and budding. It is widely appreciated that cellular post-translational modifications (PTMs) regulate protein activity within cells; however, little is known about how PTMs influence HIV replication. Previously, we reported that blocking deacetylation of tubulin using histone deacetylase inhibitors promoted the kinetics and efficiency of early postentry viral events. To uncover addnl. PTMs that modulate entry and early post-entry stages in HIV infection, we employed a flow cytometric approach to assess a panel of small mol. inhibitors on viral fusion and LTR promoterdriven gene expression. Results: While viral fusion was not significantly affected, early post-entry viral events were modulated by drugs targeting multiple processes including histone deacetylation, methylation, and bromodomain inhibition. Most notably, we observed that inhibitors of the Rho GTPase family of cytoskeletal regulators-including RhoA, Cdc42, and Rho-associated kinase signaling pathways-significantly reduced viral infection. Using phosphoproteomics and a biochem. GTPase activation assay, we found that virion-induced signaling via CD4 and CCR5 activated Rho family GTPases including Rac1 and Cdc42 and led to widespread modification of GTPase signaling-associated factors. Conclusions: Together, these data demonstrate that HIV signaling activates members of the Rho GTPase family of cytoskeletal regulators that are required for optimal HIV infection of primary CD4+ T cells.

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

Cordero, Diana’s team published research in Current Pharmaceutical Biotechnology in 15 | CAS: 71203-35-5

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, Category: pyrazoles-derivatives.

Cordero, Diana published the artcileSmall Molecule Inhibitors Limit Endothelial Cell Invasion by Staphylococcus aureus, Category: pyrazoles-derivatives, the publication is Current Pharmaceutical Biotechnology (2014), 15(8), 727-737, database is CAplus and MEDLINE.

Staphylococcus aureus is a leading causative agent in sepsis, endocarditis, and pneumonia. An emerging concept is that prognosis worsens when the infecting S. aureus strain has the capacity to not only colonize tissue as an extracellular pathogen, but to invade host cells and establish intracellular bacterial populations. In previous work, we identified host CDC42 as a central regulator of endothelial cell invasion by S. aureus. In the current work, we report that ML 141, a first-in-class CDC42 inhibitor, decreases invasion and resultant pathogenesis in a dose-dependent and reversible manner. Inhibition was found to be due in part to decreased remodeling of actin that potentially drives endocytic uptake of bacteria/fibronectin/integrin complexes. ML 141 decreased binding to fibronectin at these complexes, thereby limiting a key pathogenic mechanism used by S. aureus to invade. Structural analogs of ML 141 were synthesized (designated as the RSM series) and a subset identified that inhibit invasion through non-cytotoxic and non-bactericidal mechanisms. Our results support the development of adjunctive therapeutics targeting host CDC42 for mitigating invasive infection at the level of the host.

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