Tag: M.W=400-450

Azad, Abul K. published the artcileFGD5 regulates endothelial cell PI3 kinase-β to promote neo-angiogenesis, COA of Formula: C22H21N3O3S, the publication is FASEB Journal (2022), 36(1), e22080, database is CAplus and MEDLINE.

Angiogenesis is required in embryonic development and tissue repair in the adult. Vascular endothelial growth factor (VEGF) initiates angiogenesis, and VEGF or its receptor is targeted therapeutically to block pathol. angiogenesis. Addnl. pro-angiogenic cues, such as CXCL12 acting via the CXCR4 receptor, cooperate with VEGF/VEGFR2 to cue vascular patterning. We studied the role of FGD5, an endothelial Rho GTP/GDP exchange factor (RhoGEF), to regulate CXCR4-dependent signals in the endothelial cell (EC). Patient-derived renal cell carcinomas produce a complex milieu of growth factors that stimulated sprouting angiogenesis and endothelial tip cell differentiation ex vivo that was blocked by EC FGD5 loss. In a simplified model, CXCL12 augmented sprouting and tip gene expression under conditions where VEGF was limiting. CXCL12-stimulated tip cell differentiation was dependent on PI3 kinase (PI3K)-β activity. Knockdown of EC FGD5 abolished CXCR4 signaling to PI3K-β and Akt. Further, inhibition of Rac1, a Rho GTPase required for PI3K-β activity, recapitulated the signaling defects of FGD5 deficiency, suggesting that FGD5 may regulate PI3K-β activity through Rac1. Overexpression of a RhoGEF deficient, Dbl domain-deleted FGD5 mutant reduced CXCL12-stimulated Akt phosphorylation and failed to rescue PI3K signaling in native FGD5-deficient EC, indicating that FGD5 RhoGEF activity is required for FDG5 function. Endothelial expression of mutant PI3K-β with an inactivated Rho binding domain confirmed that CXCL12-stimulated PI3K activity in EC requires Rac1-GTP co-regulation. Together, this data identify the role of FGD5 to generate Rac1-GTP to regulate pro-angiogenic CXCR4-dependent PI3K-β signaling in EC. Inhibition of FGD5 activity may complement current angiogenesis inhibitor drugs.

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 C22H21N3O3S, COA of Formula: C22H21N3O3S.

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

Eaton, Amity F. published the artcileExpansion and contraction of the umbrella cell apical junctional ring in response to bladder filling and voiding, Safety of 4-(5-(4-Methoxyphenyl)-3-phenyl-4,5-dihydro-1H-pyrazol-1-yl)benzenesulfonamide, the publication is Molecular Biology of the Cell (2019), 30(16), 2037-2052, database is CAplus and MEDLINE.

The epithelial junctional complex, composed of tight junctions, adherens junctions, desmosomes, and an associated actomyosin cytoskeleton, forms the apical junctional ring (AJR), which must maintain its continuity in the face of external mech. forces that accompany normal physiol. functions. The AJR of umbrella cells, which line the luminal surface of the bladder, expands during bladder filling and contracts upon voiding; however, the mechanisms that drive these events are unknown. Using native umbrella cells as a model, we observed that the umbrella cell’s AJR assumed a nonsarcomeric organization in which filamentous actin and ACTN4 formed unbroken continuous rings, while nonmuscle myosin II (NMMII) formed linear tracts along the actin ring. Expansion of the umbrella cell AJR required formin-dependent actin assembly, but was independent of NMMII ATPase function. AJR expansion also required membrane traffic, RAB13-dependent exocytosis, specifically, but not trafficking events regulated by RAB8A or RAB11A. In contrast, the voiding-induced contraction of the AJR depended on NMMII and actin dynamics, RHOA, and dynamin-dependent endocytosis. Taken together, our studies indicate that a mechanism by which the umbrella cells retain continuity during cyclical changes in volume is the expansion and contraction of their AJR, processes regulated by the actomyosin cytoskeleton and membrane trafficking events.

Molecular Biology of the Cell 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, Safety 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

Hemshekhar, Mahadevappa published the artcileHost defense peptide LL-37-mediated chemoattractant properties, but not anti-inflammatory cytokine IL-1RA production, is selectively controlled by Cdc42 Rho GTPase via G protein-coupled receptors and JNK mitogen-activated protein kinase, Computed Properties of 71203-35-5, the publication is Frontiers in Immunology (2018), 1871/1-1871/17, database is CAplus and MEDLINE.

The human host defense peptide LL-37 promotes immune activation such as induction of chemokine production and recruitment of leukocytes. Conversely, LL-37 also medi-ates anti-inflammatory responses such as production of anti-inflammatory cytokines, e.g., IL-1RA, and the control of pro-inflammatory cytokines, e.g., TNF. The mechanisms regulating these disparate immunomodulatory functions of LL-37 are not completely understood. Rho GTPases are GTP-binding proteins that promote fundamental immune functions such as chemokine production and recruitment of leukocytes. However, recent studies have shown that distinct Rho proteins can both neg. and pos. regulate inflammation. Therefore, we interrogated the role of Rho GTPases in LL-37-mediated immunomodulation. We demonstrate that LL-37-induced production of chemokines, e.g., GRO-α and IL-8 is largely dependent on Cdc42/Rac1 Rho GTPase, but indepen-dent of the Ras pathway. In contrast, LL-37-induced production of the anti-inflammatory cytokine IL-1RA is not dependent on either Cdc42/Rac1 RhoGTPase or Ras GTPase. Functional studies confirmed that LL-37-induced recruitment of leukocytes (monocytes and neutrophils) is also dependent on Cdc42/Rac1 RhoGTPase activity. We demonstrate that Cdc42/Rac1-dependent bioactivity of LL-37 involves G-protein-coupled receptors (GPCR) and JNK mitogen-activated protein kinase (MAPK) signaling, but not p38 or ERK MAPK signaling. We further show that LL-37 specifically enhances the activity of Cdc42 Rho GTPase, and that the knockdown of Cdc42 suppresses LL-37-induced production of chemokines without altering the peptide’s ability to induce IL-1RA. This is the first study to demonstrate the role of Rho GTPases in LL-37-mediated responses. We demonstrate that LL-37 facilitates chemokine production and leukocyte recruitment engaging Cdc42/Rac1 Rho GTPase via GPCR and the JNK MAPK pathway. In contrast, LL-37-mediated anti-inflammatory cytokine IL-1RA production is independent of either Rho or Ras GTPase. The results of this study suggest that Cdc42 Rho GTPase may be the mol. switch that controls the opposing functions of LL-37 in the process of inflammation.

Frontiers in Immunology 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, Computed Properties of 71203-35-5.

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

Pereyaslova, D. G. published the artcileOrganic luminophors of the pyrazoline series – luminescent constituents of fluorescent pigments, Application of 4-(5-(4-Methoxyphenyl)-3-phenyl-4,5-dihydro-1H-pyrazol-1-yl)benzenesulfonamide, the publication is Ukrainskii Khimicheskii Zhurnal (Russian Edition) (1979), 45(6), 553-6, database is CAplus.

The addition of 3-(4-difluoromethylsulfonylphenyl)-1,5-diphenyl-Δ²-pyrazoline (I) [61102-38-3] to aminosulfonyltoluene-formaldehyde-melamine copolymer (II) [39277-28-6] gave a bright yellow fluorescent pigment with strong light absorption at 564 nm. When I and Rhodamine S [12627-64-4] were added to II the resulting orange-red pigment absorbed strongly at 609 nm. Similarly, a green fluorescent pigment was obtained by adding 1,4-bis[1,5-diphenyl-Δ²-3-pyrazolinyl]benzene [71203-34-4] and Direct Lightfast Turquoise K [50642-57-4] to II. Other shades of pigments were prepared by adding 1-(4-difluoromethylsulfonylphenyl)-3,5-diphenyl-Δ²-pyrazoline [61102-37-2], or pyrazoline sulfonate III, X = H, H₂NSO₂, or C₁₇H₃₅CONHSO₂ (IV) to II. The synthesis of III (X = H) or III (X = H₂NSO₂) involved reacting sulfonated 4-methoxybenzalacetophenone with PhN:NH [100-63-0] or 4-H₂NSO₂C₆H₄N:NH [4392-54-5], resp. Refluxing III (X = H₂NSO₂) with stearic chloride [112-76-5] gave IV.

Ukrainskii Khimicheskii Zhurnal (Russian Edition) 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

Kuhn, Sonja published the artcileActin Assembly around the Shigella-Containing Vacuole Promotes Successful Infection, Application In Synthesis of 71203-35-5, the publication is Cell Reports (2020), 31(6), 107638, database is CAplus and MEDLINE.

The enteroinvasive bacterium Shigella flexneri forces its uptake into non-phagocytic host cells through the translocation of T3SS effectors that subvert the actin cytoskeleton. Here, we report de novo actin polymerization after cellular entry around the bacterium-containing vacuole (BCV) leading to the formation of a dynamic actin cocoon. This cocoon is thicker than any described cellular actin structure and functions as a gatekeeper for the cytosolic access of the pathogen. Host CDC42, TOCA-1, N-WASP, WIP, the Arp2/3 complex, cortactin, coronin, and cofilin are recruited to the actin cocoon. They are subverted by T3SS effectors, such as IpgD, IpgB1, and IcsB. IcsB immobilizes components of the actin polymerization machinery at the BCV dependent on its fatty acyltransferase activity. This represents a unique microbial subversion strategy through localized entrapment of host actin regulators causing massive actin assembly. We propose that the cocoon promotes subsequent invasion steps for successful Shigella infection.

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, Application In Synthesis of 71203-35-5.

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

Rather, Imran Ibni Gani published the artcileExploration of potential role of Rho GTPase in nicotine dependence-induced withdrawal syndrome in mice, Product Details of C22H21N3O3S, the publication is Environmental Science and Pollution Research (2022), 29(12), 17417-17424, database is CAplus and MEDLINE.

The RhoA gene showed an important genotypic association with nicotine dependence and smoking initiation. The current study aims to investigate the effect of the Rho GTPase inhibitor ML141 in the progression of nicotine dependence in a mice model of precipitated nicotine withdrawal syndrome by mecamylamine. The exptl. procedure involved administration of 2.5 mg/kg nicotine dissolved in normal saline s.c. (s.c) four times a day consecutively for 7 days and last single dose in the morning on 8th day. ML-141 was dissolved in DMSO (DMSO) and was administered daily with nicotine as corrective treatment at a dose of 1,5 and 10 mg/kg (p < 0.05). An injection of 3 mg/kg of mecamylamine i.p. (i.p.) was given an hour later than the last nicotine dose on the day 8 to precipitate withdrawal of nicotine and withdrawal severity was assessed by measuring hyperalgesia, piloerection, jumping frequency, tremors, and withdrawal severity score (WSS). Various behavioral changes such as hyperalgesia, piloerection, jumping frequency, and tremors were monitored and WSS was calculated ML-141 a selective Rho GTPase inhibitor was found to show dose-dependent effect on all these parameters. Inhibition of Rho GTPase was found to reduce the severity of withdrawal syndrome; therefore, it can be concluded that Rho GTPase would serve as a suitable biol. target by regulating the reward system in brain and could be used as new target for drug discovery.

Environmental Science and Pollution Research 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, Product Details of C22H21N3O3S.

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

Sheshachalam, Avinash published the artcileThe effect of Rho drugs on mast cell activation and degranulation, Category: pyrazoles-derivatives, the publication is Journal of Leukocyte Biology (2017), 102(1), 71-81, database is CAplus and MEDLINE.

Mast cells are tissue-resident immune cells that produce potent proinflammatory mediators, which are stored in cytoplasmic granules. Stimulation triggers degranulation, a process that mobilizes granules to dock and fuse to the plasma membrane, releasing mediators. Mast cell degranulation has an important role in immunity but can also intensify inflammation and contribute to allergic disorders. Hence, it is important to understand signaling pathways that regulate mast cell degranulation. Here, we examined the role of Rho proteins in regulating mast cell activation leading to degranulation. RBL-2H3 cells and bone marrow-derived mast cells (BMMCs) were stimulated through aggregation of FcεRI receptors. Stimulated cells showed a large increase in the levels of activated Rac and, to a lesser extent, RhoA. Drugs were used to acutely inhibit the function of specific Rho proteins. The Rac inhibitor EHT-1864 and the RhoA inhibitor rhosin inhibited degranulation. Microscopic characterization showed that, upon stimulation, RBL-2H3 cells formed surface ridges that grew into large protrusions reminiscent of circular dorsal ruffles, which flattened into large lamellipodia. LysoTracker-labeled cells showed granules stream into peripheral protrusions. EHT-1864 reduced granule motility, whereas rhosin increased motility; both drugs affected the formation of peripheral protrusions. These results showed that, in response to stimuli, Rho proteins control discrete cytoskeletal remodeling processes that are needed for granule exocytosis. Rac is required to stimulate the remodeling of mast cells, triggering actin-mediated flattening of the cell periphery to create an active degranulation zone, whereas RhoA controls the streaming of highly motile granules into the active zone.

Journal of Leukocyte Biology 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 C22H32O2, Category: pyrazoles-derivatives.

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