Tag: M.W=400-450

Causer, Adam J. published the artcileCFTR limits F-actin formation and promotes morphological alignment with flow in human lung microvascular endothelial cells, Application In Synthesis of 307510-92-5, the publication is Physiological Reports (2021), 9(23), e15128, database is CAplus and MEDLINE.

Micro- and macrovascular endothelial dysfunction in response to shear stress has been observed in cystic fibrosis (CF), and has been associated with inflammation and oxidative stress. We tested the hypothesis that the cystic fibrosis transmembrane conductance regulator (CFTR) regulates endothelial actin cytoskeleton dynamics and cellular alignment in response to flow. Human lung microvascular endothelial cells (HLMVEC) were cultured with either the CFTR inhibitor GlyH-101 (20μM) or CFTRinh-172 (20μM), tumor necrosis factor (TNF)-α (10 ng/mL) or a vehicle control (0.1% DMSO) during 24 and 48 h of exposure to shear stress (11.1 dynes/cm²) or under static control conditions. Cellular morphol. and filamentous actin (F-actin) were assessed using immunocytochem. [Nitrite] and endothelin-1 ([ET-1]) were determined in cell culture supernatant by ozone-based chemiluminescence and ELISA, resp. Treatment of HLMVECs with both CFTR inhibitors prevented alignment of HLMVEC in the direction of flow after 24 and 48 h of shear stress, compared to vehicle control (both p < 0.05). Treatment with TNF-α significantly increased total F-actin after 24 h vs. control (p < 0.05), an effect that was independent of shear stress. GlyH-101 significantly increased F-actin after 24 h of shear stress vs. control (p < 0.05), with a significant (p < 0.05) reduction in cortical F-actin under both static and flow conditions. Shear stress decreased [ET-1] after 24 h (p < 0.05) and increased [nitrite] after 48 h (p < 0.05), but neither [nitrite] nor [ET-1] was affected by GlyH-101 (p > 0.05). CFTR appears to limit cytosolic actin polymerization, while maintaining a cortical rim actin distribution that is important for maintaining barrier integrity and promoting alignment with flow, without effects on endothelial nitrite or ET-1 production

Physiological Reports published new progress about 307510-92-5. 307510-92-5 belongs to thiazolidine, auxiliary class Membrane Transporter/Ion Channel,CFTR, name is 4-((4-Oxo-2-thioxo-3-(3-(trifluoromethyl)phenyl)thiazolidin-5-ylidene)methyl)benzoic acid, and the molecular formula is C18H10F3NO3S2, Application In Synthesis of 307510-92-5.

Referemce:
https://en.wikipedia.org/wiki/Thiazolidine,
Thiazolidine – ScienceDirect.com

Martinovich, Kelly M. published the artcileInvestigating the implications of CFTR exon skipping using a Cftr exon 9 deleted mouse model, Related Products of thiazolidine, the publication is Frontiers in Pharmacology (2022), 868863, database is CAplus and MEDLINE.

Severity and disease progression in people with Cystic Fibrosis (CF) is typically dependent on their genotype. One potential therapeutic strategy for people with specific mutations is exon skipping with antisense oligonucleotides (AO). CFTR exon 9 is an in-frame exon and hence the exclusion of this exon would excise only 31 amino acids but not alter the reading frame of the remaining mRNA. Splice mutations 1209 + 1 G > C and 1209 + 2 T > G were documented to cause CFTR exon 9 skipping and these variants were reported to manifest as a milder CF disease, therefore exon 9 skipping could be beneficial for people with class I mutations that affect exon 9 such as p.Trp401X. While the impact of exon 9 skipping on gene expression and cellular pathways can be studied in cells in vitro, trace amount of full-length normal or mutated material could confound the evaluation. To overcome this limitation, the impact of CFTR exon 9 skipping on disease phenotype and severity is more effectively evaluated in a small animal model. It was hypothesised that antisense oligonucleotide-mediated skipping this particular exon could result in a “mild mouse CF phenotype”. Cftr exon 9 deleted mice were generated using homologous recombination. Survival of homozygous (CftrΔ9/Δ9) and heterozygous (CftrΔ9/+) mice was compared to that of other CF mouse models, and lung and intestinal organ histol. examined for any pathologies. Primary airway epithelial cells (pAECs) were harvested from CftrΔ9/Δ9 mice and cultured at the Air Liquid Interface for CFTR functional assessment using Ussing Chamber anal. A CftrΔ9/Δ9 mouse model presented with intestinal obstructions, and at time of weaning (21 days). CftrΔ9/Δ9 mice had a survival rate of 83% that dropped to 38% by day 50. Histol. sections of the small intestine from CftrΔ9/Δ9 mice showed more goblet cells and mucus accumulation than samples from the CftrΔ9/+ littermates. Airway epithelial cell cultures established from CftrΔ9/Δ9 mice were not responsive to forskolin stimulation. The effect of Cftr exon 9 deletion on Cftr function was assessed and it was determined that the encoded Cftr isoform did not result in a milder “mouse CF disease phenotype,” suggesting that Cftr exon 9 is not dispensable, although further investigation in human CF pAECs would be required to confirm this observation.

Frontiers in Pharmacology published new progress about 307510-92-5. 307510-92-5 belongs to thiazolidine, auxiliary class Membrane Transporter/Ion Channel,CFTR, name is 4-((4-Oxo-2-thioxo-3-(3-(trifluoromethyl)phenyl)thiazolidin-5-ylidene)methyl)benzoic acid, and the molecular formula is C18H10F3NO3S2, Related Products of thiazolidine.

Referemce:
https://en.wikipedia.org/wiki/Thiazolidine,
Thiazolidine – ScienceDirect.com

Yang, Ning published the artcileChloroquine stimulates Cl- secretion by Ca2+ activated Cl- channels in rat ileum, Safety of 4-((4-Oxo-2-thioxo-3-(3-(trifluoromethyl)phenyl)thiazolidin-5-ylidene)methyl)benzoic acid, the publication is PLoS One (2014), 9(1), e87627/1-e87627/7, 7 pp., database is CAplus and MEDLINE.

Chloroquine (CQ), a bitter tasting drug widely used in treatment of malaria, is associated gastrointestinal side effects including nausea or diarrhea. In the present study, we investigated the effect of CQ on electrolyte transport in rat ileum using the Ussing chamber technique. The results showed that CQ evoked an increase in short circuit current (ISC) in rat ileum at lower concentration (≤5 × 10-4 M) but induced a decrease at higher concentrations (≥10-3 M). These responses were not affected by tetrodotoxin (TTX). Other bitter compounds, such as denatoniumbenzoate and quinine, exhibited similar effects. CQ-evoked increase in ISC was partly reduced by amiloride(10-4 M), a blocker of epithelial Na+ channels. Furosemide (10-4 M), an inhibitor of Na+-K+-2Cl- co-transporter, also inhibited the increased ISC response to CQ, whereas another Cl- channel inhibitor, CFTR(inh)-172(10-5 M), had no effect. Intriguingly, CQ-evoked increases were almost completely abolished by niflumic acid (10-4 M), a relatively specific Ca2+-activated Cl- channel (CaCC) inhibitor. Furthermore, other CaCC inhibitors, such as DIDS and NPPB, also exhibited similar effects. CQ-induced increases in ISC were also abolished by thapsigargin(10-6 M), a Ca2+ pump inhibitor and in the absence of either Cl- or Ca2+ from bathing solutions Further studies demonstrated that T2R and CaCC-TMEM16A were colocalized in small intestinal epithelial cells and the T2R agonist CQ evoked an increase of intracelluar Ca2+ in small intestinal epithelial cells. Taken together, these results demonstrate that CQ induces Cl- secretion in rat ileum through CaCC at low concentrations, suggesting a novel explanation for CQ-associated gastrointestinal side-effects during the treatment of malaria.

PLoS One published new progress about 307510-92-5. 307510-92-5 belongs to thiazolidine, auxiliary class Membrane Transporter/Ion Channel,CFTR, name is 4-((4-Oxo-2-thioxo-3-(3-(trifluoromethyl)phenyl)thiazolidin-5-ylidene)methyl)benzoic acid, and the molecular formula is C8H19NO2, Safety of 4-((4-Oxo-2-thioxo-3-(3-(trifluoromethyl)phenyl)thiazolidin-5-ylidene)methyl)benzoic acid.

Referemce:
https://en.wikipedia.org/wiki/Thiazolidine,
Thiazolidine – ScienceDirect.com

Liu, Mingfeng published the artcileTreatment of human T-cell acute lymphoblastic leukemia cells with CFTR inhibitor CFTRinh-172, Category: thiazolidine, the publication is Leukemia Research (2019), 106225, database is CAplus and MEDLINE.

Our previous studies have demonstrated that a previously unrecognized role of CFTR in hematopoiesis and acute leukemia. Here, we show that CFTR inhibitor CFTR-inh172 possesses ability to inhibit human T-cell acute lymphoblastic leukemia cells. In detail, CFTR-inh172 inhibited cell proliferation, promoted apoptosis and arrested the cell cycle in human T-cell acute lymphoblastic leukemia cell CCRF-CEM, JURKAT and MOLT-4. Furthermore, transcriptome anal. reveals that CFTR-inh172 induces significant alteration of gene expression related to apoptosis and proliferation. These findings demonstrate the potential of CFTR inhibitor CFTR-inh172 in human T-cell acute lymphoblastic leukemia treatment.

Leukemia Research published new progress about 307510-92-5. 307510-92-5 belongs to thiazolidine, auxiliary class Membrane Transporter/Ion Channel,CFTR, name is 4-((4-Oxo-2-thioxo-3-(3-(trifluoromethyl)phenyl)thiazolidin-5-ylidene)methyl)benzoic acid, and the molecular formula is C18H10F3NO3S2, Category: thiazolidine.

Referemce:
https://en.wikipedia.org/wiki/Thiazolidine,
Thiazolidine – ScienceDirect.com

Wang, Jia published the artcileIncreased intracellular Cl^– concentration by activating FAK promotes airway epithelial BEAS-2B cells proliferation and wound healing, Computed Properties of 307510-92-5, the publication is Archives of Biochemistry and Biophysics (2020), 108225, database is CAplus and MEDLINE.

An increase in intracellular Cl^– concentration ([Cl^–]_i) may be a general response of airway epithelial cells to various stimuli and may participate in some basic cellular functions. However, whether the basic functional activities of cells, such as proliferation and wound healing, are related to Cl^– activities remains unclear. This study aimed to investigate the effects and potential mechanisms of [Cl^–]_i on the proliferation and wound healing ability of airway epithelial BEAS-2B cells. BEAS-2B cells were treated with four Cl^– channel inhibitors (T16Ainh-A01, CFTRinh-172, CaCCinh-A01, and IAA-94), and the Cl^– fluorescence probe N-(ethoxycarbonylmethyl)-6-methoxyquinolinium bromide was used. Results showed that all Cl^– channel inhibitors could increase [Cl^–]_i in BEAS-2B cells. The increased [Cl^–]_i induced by Cl^– channel inhibitors or clamping [Cl^–]_i at high levels enhanced the phosphorylation of focal adhesion kinase (FAK) and subsequently promoted the proliferation and wound healing ability of BEAS-2B cells. By contrast, the FAK inhibitor PF573228 abrogated these effects induced by the increased [Cl^–]_i. FAK also activated the PI3K/AKT signaling pathway. In conclusion, increased [Cl^–]_i promotes the proliferation and wound healing ability of BEAS-2B cells by activating FAK to activate the PI3K/AKT signaling pathway. Intracellular Cl^– may act as a signaling mol. to regulate the proliferation and wound healing ability of airway epithelial cells.

Archives of Biochemistry and Biophysics published new progress about 307510-92-5. 307510-92-5 belongs to thiazolidine, auxiliary class Membrane Transporter/Ion Channel,CFTR, name is 4-((4-Oxo-2-thioxo-3-(3-(trifluoromethyl)phenyl)thiazolidin-5-ylidene)methyl)benzoic acid, and the molecular formula is C31H25F2N5O7S, Computed Properties of 307510-92-5.

Referemce:
https://en.wikipedia.org/wiki/Thiazolidine,
Thiazolidine – ScienceDirect.com

Wang, Xiaofei published the artcilePredominant constitutive CFTR conductance in small airways, Computed Properties of 307510-92-5, the publication is Respiratory Research (2005), 6(1), No pp. given, database is CAplus and MEDLINE.

Background: The pathol. hallmarks of chronic obstructive pulmonary disease (COPD) are inflammation of the small airways (bronchiolitis) and destruction of lung parenchyma (emphysema). These forms of disease arise from chronic prolonged infections, which are usually never present in the normal lung. Despite the fact that primary hygiene and defense of the airways presumably requires a well controlled fluid environment on the surface of the bronchiolar airway, very little is know of the fluid and electrolyte transport properties of airways of less than a few mm diameter Methods: We introduce a novel approach to examine some of these properties in a preparation of minimally traumatized porcine bronchioles of about 1 mm diameter by microperfusing the intact bronchiole. Results: In bilateral isotonic NaCl Ringer solutions, the spontaneous transepithelial potential (TEP; lumen to bath) of the bronchiole was small (mean+sem: -3± mV; n=25), but when gluconate replaced luminal Cl^– the bionic Cl^– diffusion potentials (-58±3 mV; n=25) were as large as -90 mV. TEP diffusion potentials from 2:1 NaCl dilution showed that epithelial Cl^– permeability was at least 5 times greater than Na⁺ permeability. The anion selectivity sequence was similar to that of CFTR. The bionic TEP became more electroneg. with stimulation by luminal forskolin (5 μM)+IBMX (100 μM), ATP (100 μM), or adenosine (100 μM), but not by ionomycin. The TEP was partially inhibited by NPPB (100 μM), GlyH-101* (5-50 μM), and CFTR_Inh-172* (5 μM). RT-PCR gave identifying products for CFTR, α-, β-, and γ-ENaC and NKCCl. Antibodies to CFTR localized specifically to the epithelial cells lining the lumen of the small airways. Conclusion: These results indicate that the small airway of the pig is characterized by a constitutively active Cl^– conductance that is most likely due to CFTR.

Respiratory Research published new progress about 307510-92-5. 307510-92-5 belongs to thiazolidine, auxiliary class Membrane Transporter/Ion Channel,CFTR, name is 4-((4-Oxo-2-thioxo-3-(3-(trifluoromethyl)phenyl)thiazolidin-5-ylidene)methyl)benzoic acid, and the molecular formula is C40H35N7O8, Computed Properties of 307510-92-5.

Referemce:
https://en.wikipedia.org/wiki/Thiazolidine,
Thiazolidine – ScienceDirect.com

Valdivieso, Angel G. published the artcileMeasurement of cystic fibrosis transmembrane conductance regulator activity using fluorescence spectrophotometry, Category: thiazolidine, the publication is Analytical Biochemistry (2011), 418(2), 231-237, database is CAplus and MEDLINE.

Cystic fibrosis (CF) is a frequent autosomal recessive disease caused by mutations that impair the CF transmembrane conductance regulator (CFTR) protein function. CFTR is a chloride channel activated by cAMP via protein kinase A (PKA) and ATP hydrolysis. The authors describe here a method to measure CFTR activity in a monolayer of cultured cells using a fluorescence spectrophotometer and the chloride-sensitive probe 6-methoxy-N-(3-sulfopropyl)quinolinium (SPQ). Modifying a slice holder, the spectrophotometer quartz cuvette was converted in a perfusion chamber, allowing measurement of CFTR activity in real time, in a monolayer of T84 colon carcinoma cells. The SPQ Stern-Volmer constant (K_Cl^–) for chloride in water solution was 115.0±2.8 M^-1, whereas the intracellular K_Cl^– was 17.8±0.8 M^-1, for T84 cells. A functional anal. was performed by measuring CFTR activity in T84 cells. The CFTR transport inhibitors CFTR(inh)-172 (5 μM) and glibenclamide (100 μM) showed a significant reduction (P < 0.05) in CFTR activity. This simple method allows measuring CFTR activity in a very simple, reproducible, and sensitive way.

Analytical Biochemistry published new progress about 307510-92-5. 307510-92-5 belongs to thiazolidine, auxiliary class Membrane Transporter/Ion Channel,CFTR, name is 4-((4-Oxo-2-thioxo-3-(3-(trifluoromethyl)phenyl)thiazolidin-5-ylidene)methyl)benzoic acid, and the molecular formula is C13H16O2, Category: thiazolidine.

Referemce:
https://en.wikipedia.org/wiki/Thiazolidine,
Thiazolidine – ScienceDirect.com