Month: November 2022

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

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

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

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

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

Akiba, Yasutada published the artcileA novel small molecule CFTR inhibitor attenuates HCO₃^– secretion and duodenal ulcer formation in rats, Application In Synthesis of 307510-92-5, the publication is American Journal of Physiology (2005), 289(4), G753-G759, database is CAplus and MEDLINE.

The cystic fibrosis (CF) transmembrane conductance regulator (CFTR) plays a crucial role in mediating duodenal bicarbonate (HCO₃^–) secretion (DBS). Although impaired DBS is observed in CF mutant mice and in CF patients, which would predict increased ulcer susceptibility, duodenal injury is rarely observed in CF patients and is reduced in CF mutant mice. To explain this apparent paradox, we hypothesized that CFTR dysfunction increases cellular [HCO₃^–] and buffering power. To further test this hypothesis, we examined the effect of a novel, potent, and highly selective CFTR inhibitor, CFTR_inh-172, on DBS and duodenal ulceration in rats. DBS was measured in situ using a standard loop perfusion model with a pH stat under isoflurane anesthesia. Duodenal ulcers were induced in rats by cysteamine with or without CFTR_inh-172 pretreatment 1 h before cysteamine. Superfusion of CFTR_inh-172 (0.1-10 μM) over the duodenal mucosa had no effect on basal DBS but at 10 μM inhibited acid-induced DBS, suggesting that its effect was limited to CFTR activation. Acid-induced DBS was abolished at 1 and 3 h and was reduced 24 h after treatment with CFTR_inh-172, although basal DBS was increased at 24 h. CFTR_inh-172 treatment had no effect on gastric acid or HCO₃^– secretion. Duodenal ulcers were observed 24 h after cysteamine treatment but were reduced in CFTR_inh-172-pretreated rats. CFTR_inh-172 acutely produces CFTR dysfunction in rodents for up to 24 h. CFTR inhibition reduces acid-induced DBS but also prevents duodenal ulcer formation, supporting our hypothesis that intracellular HCO₃^– may be an important protective mechanism for duodenal epithelial cells.

American Journal of Physiology 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

Harada, Yumi published the artcileMashiningan improves opioid-induced constipation in rats by activating cystic fibrosis transmembrane conductance regulator chloride channel, COA of Formula: C18H10F3NO3S2, the publication is Journal of Pharmacology and Experimental Therapeutics (2017), 362(1), 78-84, database is CAplus and MEDLINE.

Opioid receptor stimulants are analgesics used in patients with and without cancer; however, they often cause constipation, resulting in poor adherence and deterioration of the quality of life. Hence, suitable treatments for constipation are required. In this study, we investigated the pharmacol. mechanisms of action of mashiningan (MNG), a Kampo medicine used to treat constipation, and evaluated the effect of MNG on opioid-induced constipation in rats. MNG (100 or 300 mg/kg) was orally administered to normal or codeine phosphate (CPH)-induced constipation in rats, and its effect was evaluated on the basis of fecal counts, characteristics, and weight Small intestinal fluid secretion was measured after treatment with MNG alone or coadministration with a cystic fibrosis transmembrane conductance regulator (CFTR)-specific inhibitor (CFTRinh-172). The effects of MNG on the CFTR and type-2 chloride channel were determined using patch-clamp or short-circuit current experiments, resp. MNG increased the fecal weight and proportion of soft feces in normal rats. CPH-induced constipation in rats decreased fecal counts and weight, whereas MNG prevented these effects and increased the proportion of soft feces. MNG increased the electronic chloride current, and this effect was inhibited by the CFTRinh-172 in the CFTR assay. Furthermore, MNG increased small intestinal fluid secretion, and this effect was abolished by coadministration with the CFTRinh-172. MNG improved opioid-induced constipation in rats, and this improvement may have been mediated by increasing intestinal fluid secretion via CFTR chloride channel activation. Therefore, MNG is expected as a medicine of the treatment of constipation in patients taking opioids.

Journal of Pharmacology and Experimental Therapeutics 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

Khadijah Ramli, Nur Siti published the artcileTestosterone enhances expression and functional activity of epithelial sodium channel (ENaC), cystic fibrosis transmembrane regulator (CFTR) and sodium hydrogen exchanger (NHE) in vas deferens of sex-steroid deficient male rats, Computed Properties of 307510-92-5, the publication is Steroids (2018), 117-133, database is CAplus and MEDLINE.

Effects of testosterone on expression and functional activity of ENaC, CFTR and NHE in vas deferens were investigated. Orchidectomized, adult male rats were given 125 and 250 μg/kg/day testosterone s.c., with or without flutamide and finasteride for seven consecutive days. At the end of the treatment, rats were anesthetized and vas deferens were perfused. Changes in vas deferens fluid secretion rate, pH, HCO₃^–, Cl^– and Na⁺ concentrations were recorded in the presence of amiloride and Cftr inh-172. Rats were then sacrificed and vas deferens were harvested and subjected for mol. biol. anal. Testosterone treatment caused the fluid pH and HCO₃^– concentrations to decrease but secretion rate, Cl^– and Na⁺ concentrations to increase, where upon amiloride administration, the pH and HCO₃^– concentration increased but Cl^– and Na⁺ concentrations further increased. In testosterone-treated rats, administration of Cftr inh-172 caused all fluid parameters to decrease. In testosterone-treated rats co-administered with flutamide or finasteride, pH and HCO₃^– concentration increased but fluid secretion rate, Cl^– and Na⁺ concentrations decreased and these parameters were not affected by amiloride or Cftr inh-172 administration. Under testosterone influence, CFTR and γ-ENaC were highly expressed at the apical membrane while NHE-1 and 4 were highly expressed at the basolateral membrane of vas deferens epithelium. Meanwhile, NHE-2 and 3 were highly expressed at the apical membrane. Differential expression of ENaC, CFTR and NHE in vas deferens under testosterone influence indicated the important role of these transporters in creating optimal fluid microenvironment that is essential for preserving male fertility.

Steroids 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

Billet, Arnaud published the artcileDevelopment of automated patch clamp technique to investigate CFTR chloride channel function, Formula: C18H10F3NO3S2, the publication is Frontiers in Pharmacology (2017), 195/1-195/10, database is CAplus and MEDLINE.

The chloride (Cl-) channel cystic fibrosis transmembrane conductance regulator (CFTR) is defective in cystic fibrosis (CF), and mutation of its encoding gene leads to various defects such as retention of the misfolded protein in the endoplasmic reticulum, reduced stability at the plasma membrane, abnormal channel gating with low open probability, and thermal instability, which leads to inactivation of the channel at physiol. temperature Pharmacotherapy is one major therapeutic approach in the CF field and needs sensible and fast tools to identify promising compounds The high throughput screening assays available are often fast and sensible techniques but with lack of specificity. Few works used automated patch clamp (APC) for CFTR recording, and none have compared conventional and planar techniques and demonstrated their capabilities for different types of experiments In this study, we evaluated the use of planar parallel APC technique for pharmacol. search of CFTR-trafficking correctors and CFTR function modulators. Using optimized conditions, we recorded both wt- and corrected F508del-CFTR Cl- currents with automated whole-cell patch clamp and compared the data to results obtained with conventional manual whole-cell patch clamp. We found no significant difference in patch clamp parameters such as cell capacitance and series resistance between automated and manual patch clamp. Also, the results showed good similarities of CFTR currents recording between the two methods. We showed that similar stimulation protocols could be used in both manual and automatic techniques allowing precise control of temperature, classic I/V relationship, and monitoring of current stability in time. In conclusion, parallel patch-clamp recording allows rapid and efficient investigation of CFTR currents with a variety of tests available and could be considered as new tool for medium throughput screening in CF pharmacotherapy.

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, Formula: C18H10F3NO3S2.

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

Garcia, Rocio published the artcileCFTR chloride channel activity modulates the mitochondrial morphology in cultured epithelial cells, Recommanded Product: 4-((4-Oxo-2-thioxo-3-(3-(trifluoromethyl)phenyl)thiazolidin-5-ylidene)methyl)benzoic acid, the publication is International Journal of Biochemistry & Cell Biology (2021), 105976, database is CAplus and MEDLINE.

The impairment of the CFTR channel activity, a cAMP-activated chloride (Cl-) channel responsible for cystic fibrosis (CF), has been associated with a variety of mitochondrial alterations such as modified gene expression, impairment in oxidative phosphorylation, increased reactive oxygen species (ROS), and a disbalance in calcium homeostasis. The mechanisms by which these processes occur in CF are not fully understood. Previously, we demonstrated a reduced MTND4 expression and a failure in the mitochondrial complex I (mCx-I) activity in CF cells. Here we hypothesized that the activity of CFTR might modulate the mitochondrial fission/fusion balance, explaining the decreased mCx-I. The mitochondrial morphol. and the levels of mitochondrial dynamic proteins MFN1 and DRP1 were analyzed in IB3-1 CF cells, and S9 (IB3-1 expressing wt-CFTR), and C38 (IB3-1 expressing a truncated functional CFTR) cells. The mitochondrial morphol. of IB3-1 cells compared to S9 and C38 cells showed that the impaired CFTR activity induced a fragmented mitochondrial network with increased rounded mitochondria and shorter branches. Similar results were obtained by using the CFTR pharmacol. inhibitors CFTR(inh)-172 and GlyH101 on C38 cells. These morphol. changes were accompanied by modifications in the levels of the mitochondrial dynamic proteins MFN1, DRP1, and p(616)-DRP1. IB3-1 CF cells treated with Mdivi-1, an inhibitor of mitochondrial fission, restored the mCx-I activity to values similar to those seen in S9 and C38 cells. These results suggest that the mitochondrial fission/fusion balance is regulated by the CFTR activity and might be a potential target to treat the impaired mCx-I activity in CF.

International Journal of Biochemistry & Cell Biology 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, Recommanded Product: 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