Month: November 2022

Rievaj, Juraj published the artcileAllergic sensitization enhances anion current responsiveness of murine trachea to PAR-2 activation, Related Products of thiazolidine, the publication is Pfluegers Archiv (2012), 463(3), 497-509, database is CAplus and MEDLINE.

Protease-activated receptor 2 (PAR-2) is a G protein-coupled receptor possibly involved in the pathogenesis of asthma. PAR-2 also modulates ion transport in cultured epithelial cells, but these effects in native airways are controversial. The influence of allergic inflammation on PAR-2-induced changes in ion transport has received little attention. Here, we studied immediate changes in transepithelial short circuit current (I _sc) induced by PAR-2 activation in the tracheas of naive and allergic mice. Activation of PAR-2 with an apically added activation peptide (AP) induced a small increase in I _sc, while a much larger increase was observed following basolateral AP addition In ovalbumin-sensitized and -challenged animals used as a model of allergic airway inflammation, the effect of basolateral AP addition was enhanced. Responses to basolateral AP in both naive and allergic mice were not decreased by blocking sodium absorption with amiloride or CFTR function with CFTR_inh172 but were reduced by the cyclooxygenase inhibitor indomethacin and largely blocked (>80%) by niflumic acid, a calcium-activated chloride channels’ (CaCC) blocker. Allergic mice also showed an enhanced response to ATP and thapsigargin. There was no change in mRNA expression of Par-2 or of the chloride channels Ano1 (Tmem16a) and Bestrophin 2 in tracheas from allergic mice, while mRNA levels of Bestrophin 1 were increased. In conclusion, basolateral PAR-2 activation in the mouse airways led to increased anion secretion through apical CaCC, which was more pronounced in allergic animals. This could be a protective mechanism aimed at clearing allergens and defending against mucus plugging.

Pfluegers Archiv 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

Okuda, Kenichi published the artcileSecretory cells dominate airway CFTR expression and function in human airway superficial epithelia, Computed Properties of 307510-92-5, the publication is American Journal of Respiratory and Critical Care Medicine (2021), 203(10), 1275-1289, database is CAplus and MEDLINE.

Identification of the specific cell types expressing CFTR (cystic fibrosis [CF] transmembrane conductance regulator) is required for precision medicine therapies for CF. However, a full characterization of CFTR expression in normal human airway epithelia is missing. To identify the cell types that contribute to CFTR expression and function within the proximal-distal axis of the normal human lung. Single-cell RNA (scRNA) sequencing (scRNA-seq) was performed on freshly isolated human large and small airway epithelial cells. ScRNA in situ hybridization (ISH) and single-cell qRT-PCR were performed for validation. In vitro culture systems correlated CFTR function with cell types. Lentiviruses were used for cell type-specific transduction of wild-type CFTR in CF cells. ScRNA-seq identified secretory cells as dominating CFTR expression in normal human large and, particularly, small airway superficial epithelia, followed by basal cells. Ionocytes expressed the highest CFTR levels but were rare, whereas the expression in ciliated cells was infrequent and low. scRNA ISH and single-cell qRT-PCR confirmed the scRNA-seq findings. CF lungs exhibited distributions of CFTR and ionocytes similar to those of normal control subjects. CFTR mediated Cl- secretion in cultures tracked secretory cell, but not ionocyte, densities. Furthermore, the nucleotide-purinergic regulatory system that controls CFTRmediated hydration was associated with secretory cells and not with ionocytes. Lentiviral transduction of wild-type CFTR produced CFTR-mediated Cl- secretion in CF airway secretory cells but not in ciliated cells. Secretory cells dominate CFTR expression and function in human airway superficial epithelia. CFTR therapies may need to restore CFTR function to multiple cell types, with a focus on secretory cells.

American Journal of Respiratory and Critical Care Medicine 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, Computed Properties of 307510-92-5.

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

Sui, Jin-Liang published the artcileOptimization of a Yellow Fluorescent Protein-Based Iodide Influx High-Throughput Screening Assay for Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Modulators, Product Details of C18H10F3NO3S2, the publication is Assay and Drug Development Technologies (2010), 8(6), 656-668, database is CAplus and MEDLINE.

Cystic fibrosis is an inherited, life-threatening disease associated with mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The most common mutation, F508del CFTR, is found in 90% of CF patients. The loss of a single amino acid (phenylalanine at position 508) results in malformed CFTR with defective trafficking to the plasma membrane and impaired channel function. A functional assay with cells expressing F508del CFTR has been previously described by others using genetically engineered halide-sensitive yellow fluorescent protein to screen for CFTR modulators. We adapted this yellow fluorescent protein assay to 384-well plate format with a high-throughput screening plate reader, and optimized the assay in terms of data quality, resolution, and throughput, with target-specific protocols. The optimized assay was validated with reference compounds from cystic fibrosis foundation therapeutics. On the basis of the Z-factor range (≥0.5) and the potential productivity, this assay is well suited for high-throughput screening. It was successfully used to screen for active single agent and synergistic combinations of single agent modulators of F508del CFTR from a library collection of current active pharmaceutical ingredients (supported by Cystic Fibrosis Foundation Therapeutics).

Assay and Drug Development Technologies 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 CBF6K, Product Details of C18H10F3NO3S2.

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

Chang, Jianjun published the artcileIon transport mechanisms for smoke inhalation-injured airway epithelial barrier, Category: thiazolidine, the publication is Cell Biology and Toxicology (2020), 36(6), 571-589, database is CAplus and MEDLINE.

We aimed to analyze the effects of thermal stress and smoke aldehyde on the permeability of the airway epithelial barrier. Transepithelial resistance (R_TE) and short-circuit current (I_SC) of mouse tracheal epithelial monolayers were digitized by an Ussing chamber setup. Na⁺ depletion, amiloride (an inhibitor for epithelial Na⁺ channels [ENaCs]), ouabain (a blocker for Na⁺/K⁺-ATPase), and CFTRinh-172 (a blocker of cystic fibrosis transmembrane regulator [CFTR]) altered the responses of R_TE and I_SC to thermal stress. Acrolein, one of the main oxidative unsaturated aldehydes in fire smoke, eliminated R_TE and I_SC. Na⁺ depletion, amiloride, ouabain, and CFTRinh-172 suppressed acrolein-sensitive I_SC, but showed activating effects on acrolein-sensitive R_TE. Thermal stress or acrolein disrupted zonula occludens-1 tight junctions, increased fluorescein isothiocyanate-dextran permeability but did not cause cell death or detachment. The synergistic effects of thermal stress and acrolein exacerbated the damage to monolayers. In conclusion, the paracellular pathway mediated by the tight junctions and the transcellular pathway mediated by active and passive ion transport pathways contribute to impairment of the airway epithelial barrier caused by thermal stress and acrolein.

Cell Biology and Toxicology 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

Thiagarajah, Jay R. published the artcilePrevention of toxin-induced intestinal ion and fluid secretion by a small-molecule CFTR inhibitor, Application In Synthesis of 307510-92-5, the publication is Gastroenterology (2004), 126(2), 511-519, database is CAplus and MEDLINE.

Background & Aims: The cystic fibrosis transmembrane conductance regulator (CFTR) provides an important apical route for Cl^– secretion across intestinal epithelia. A thiazolidinone-type CFTR blocker (CFTR_inh-172) reduced cholera toxin-induced fluid accumulation in mouse intestinal loops. Here, we characterize the efficacy and pharmacodynamics of CFTR_inh-172 in blocking cAMP and cGMP induced Cl^–/fluid secretion in rodent and human intestine. Methods & Results: CFTR_inh-172 inhibited cAMP and cGMP agonist induced short-circuit current by >95% in T84 colonic epithelial cells (K_I ∼ 3 μmol/L) and in mouse and human intestinal sheets (K_I ∼ 9 μmol/L). A single i.p. injection of CFTR_inh-172 (200 μg) blocked intestinal fluid secretion in a rat closed-loop model by >90% for cholera toxin and >70% for STa Escherichia coli toxin. In mice, CFTR_inh-172 (20 μg) inhibited cholera toxin-induced intestinal fluid secretion by 90% (persistence t_1/2 ∼10 h, K_I ∼ 5 μg) and STa toxin by 75% (K_I ∼ 10 μg). Tissue distribution and pharmacokinetic studies indicated intestinal CFTR_inh-172 accumulation facilitated by enterohepatic circulation. An oral CFTR_inh-172 preparation reduced fluid secretion by >90% in a mouse open-loop cholera model. Conclusions: A small mol. CFTR blocker markedly reduced intestinal ion and fluid secretion caused by cAMP/cGMP-dependent bacterial enterotoxins. CFTR inhibition may thus reduce fluid secretion in infectious secretory diarrheas.

Gastroenterology 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 C7H5FN2, Application In Synthesis of 307510-92-5.

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

Lopes-Pacheco, Miqueias published the artcileCombination of Correctors Rescue ΔF508-CFTR by Reducing Its Association with Hsp40 and Hsp27*, COA of Formula: C18H10F3NO3S2, the publication is Journal of Biological Chemistry (2015), 290(42), 25636-25645, database is CAplus and MEDLINE.

Correcting the processing of ΔF508-CFTR, the most common mutation in cystic fibrosis, is the major goal in the development of new therapies for this disease. Here, we determined whether ΔF508 could be rescued by a combination of small-mol. correctors, and identified the mechanism by which correctors rescue the trafficking mutant of cystic fibrosis transmembrane conductance regulator (CFTR). We transfected COS-7 cells with ΔF508, created HEK-293 stably expressing ΔF508, and utilized CFBE41o- cell lines stably transduced with ΔF508. As shown previously, ΔF508 expressed less protein, was unstable at physiol. temperature, and rapidly degraded. When the cells were treated with the combination C18 + C4 the mature C-band was expressed at the cell surface. After treatment with C18 + C4, we saw a lower rate of protein disappearance after translation was stopped with cycloheximide. To understand how this rescue occurs, we evaluated the change in the binding of proteins involved in endoplasmic reticulum-associated degradation, such as Hsp27 (HspB1) and Hsp40 (DnaJ). We saw a dramatic reduction in binding to heat shock proteins 27 and 40 following combined corrector therapy. The siRNA experiments confirmed that a reduction in Hsp27 or Hsp40 rescued CFTR in the ΔF508 mutant, but the rescue was not additive or synergistic with C4 + 18 treatment, indicating these correctors shared a common pathway for rescue involving a network of endoplasmic reticulum-associated degradation proteins.

Journal of Biological Chemistry 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, COA of Formula: C18H10F3NO3S2.

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

Laselva, Onofrio published the artcileRescue of multiple class II CFTR mutations by elexacaftor + tezacaftor + ivacaftor mediated in part by the dual activities of elexacaftor as both corrector and potentiator, Synthetic Route of 307510-92-5, the publication is European Respiratory Journal (2021), 57(6), 2002774, database is CAplus and MEDLINE.

Pos. results in pre-clin. studies of the triple combination of elexacaftor, tezacaftor and ivacaftor, performed in airway epithelial cell cultures obtained from patients harbouring the class II cystic fibrosis transmembrane conductance regulator (CFTR) mutation F508del-CFTR, translated to impressive clin. outcomes for subjects carrying this mutation in clin. trials and approval of Trikafta. Encouraged by this correlation, we were prompted to evaluate the effect of the elexacaftor, tezacaftor and ivacaftor triple combination on primary nasal epithelial cultures obtained from individuals with rare class II CF-causing mutations (G85E, M1101K and N1303K) for which Trikafta is not approved. Cultures from individuals homozygous for M1101K responded better than cultures harbouring G85E and N1303K after treatment with the triple combination with respect to improvement in regulated channel function and protein processing. A similar genotype-specific effect of the triple combination was observed when the different mutations were expressed in HEK293 cells, supporting the hypothesis that these modulators may act directly on the mutant proteins. Detailed studies in nasal cultures and HEK293 cells showed that the corrector, elexacaftor, exhibited dual activity as both corrector and potentiator, and suggested that the potentiator activity contributes to its pharmacol. activity. These pre-clin. studies using nasal epithelial cultures identified mutation genotypes for which elexacaftor, tezacaftor and ivacaftor may produce clin. responses that are comparable to, or inferior to, those observed for F508del-CFTR.

European Respiratory Journal 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, Synthetic Route of 307510-92-5.

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

Srivastava, Jitendra Kumar published the artcilePharmacological evaluation of hybrid thiazolidin-4-one-1,3,5-triazines for NF-κB, biofilm and CFTR activity, Name: 4-((4-Oxo-2-thioxo-3-(3-(trifluoromethyl)phenyl)thiazolidin-5-ylidene)methyl)benzoic acid, the publication is RSC Advances (2015), 5(108), 88710-88718, database is CAplus.

Cystic fibrosis (CF) is a monogenetic disease caused mostly by the F508del mutation, a deletion of phenylalanine at position 508 of the CF transmembrane conductance regulator (CFTR) protein, which causes improper localization and functioning of this chloride channel in lung, pancreas, and intestine by affecting the normal fluid homeostasis. In CF the lungs are the most affected organ due to the accumulation of thick mucus, which results into heavy bacterial load and associated chronic inflammation. Therefore, novel state-of-the-art therapies are needed to circumvent this problem. To address this, a series of compounds (thiazolidin-4-one-1,3,5-triazines) was tested for the inhibition of NF-κB, and compounds SP6 and SP5 showed most significant activity (resp. with relative NF-κB activity: 1.82 ± 1.87 and 1.96 ± 1.56). Docking studies of the active compounds in the DNA binding surface of the N-terminal domains of NF-κB were also carried out to identify which structural motifs are vital for activity. These compounds were also tested for antibiofilm activity against P. aeruginosa and S. aureus where they showed MIC ranges from 7.81-125 μg mL^-1. The most active compound – SP6 was further assayed by micro-Ussing chamber experiments to determine its CFTR inhibitory properties, given its structural similarity to CFTR Inh₁₇₂. Results suggest that SP6 does not inhibit CFTR alone or in combination with Inh₁₇₂.

RSC Advances 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 C11H8O3, Name: 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