Category: thiazolidine

Ferreira, Vera F. C. published the artcileTargeting of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Protein with a Technetium-99m Imaging Probe, SDS of cas: 307510-92-5, the publication is ChemMedChem (2018), 13(14), 1469-1478, database is CAplus and MEDLINE.

Cystic fibrosis (CF) is caused by mutations in the gene that encodes the CF transmembrane conductance regulator (CFTR) protein. The most common mutation, F508del, leads to almost total absence of CFTR at the plasma membrane, a defect potentially corrected via drug-based therapies. Herein, we report the first proof-of-principle study of a noninvasive imaging probe able to detect CFTR at the plasma membrane. We radiolabeled the CFTR inhibitor, CFTR_inh-172a, with technetium-99m via a pyrazolyl-diamine chelating unit, yielding a novel ^99mTc(CO)₃ complex. A non-radioactive surrogate showed that the structural modifications introduced in the inhibitor did not affect its activity. The radioactive complex was able to detect plasma membrane CFTR, shown by its significantly higher uptake in wild-type vs. mutated cells. Furthermore, assessment of F508del CFTR pharmacol. correction in human cells using the radioactive complex revealed differences in corrector vs. control uptake, recapitulating the biochem. correction observed for the protein.

ChemMedChem 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, SDS of cas: 307510-92-5.

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

Talbi, Khaoula published the artcileCalmodulin-Dependent Regulation of Overexpressed but Not Endogenous TMEM16A Expressed in Airway Epithelial Cells, Category: thiazolidine, the publication is Membranes (Basel, Switzerland) (2021), 11(9), 723, database is CAplus and MEDLINE.

Regulation of the Ca2+-activated Cl- channel TMEM16A by Ca²⁺/calmodulin (CAM) is discussed controversially. In the present study, we compared regulation of TMEM16A by Ca²⁺/calmodulin (holo-CAM), CAM-dependent kinase (CAMKII), and CAM-dependent phosphatase calcineurin in TMEM16A-overexpressing HEK293 cells and TMEM16A expressed endogenously in airway and colonic epithelial cells. The activator of the Ca²⁺/CAM-regulated K⁺ channel KCNN4, 1-EBIO, activated TMEM16A in overexpressing cells, but not in cells with endogenous expression of TMEM16A. Evidence is provided that CAM-interaction with TMEM16A modulates the Ca²⁺ sensitivity of the Cl- channel. Enhanced Ca²⁺ sensitivity of overexpressed TMEM16A explains its activity at basal (non-elevated) intracellular Ca²⁺ levels. The present results correspond well to a recent report that demonstrates a Ca²⁺-unbound form of CAM (apo-CAM) that is pre-associated with TMEM16A and mediates a Ca²⁺-dependent sensitization of activation (and inactivation). However, when using activators or inhibitors for holo-CAM, CAMKII, or calcineurin, we were unable to detect a significant impact of CAM, and limit evidence for regulation by CAM-dependent regulatory proteins on receptor-mediated activation of endogenous TMEM16A in airway or colonic epithelial cells. We propose that regulatory properties of TMEM16A and other members of the TMEM16 family as detected in overexpression studies, should be validated for endogenous TMEM16A and physiol. stimuli such as activation of phospholipase C (PLC)-coupled receptors.

Membranes (Basel, Switzerland) 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 C8H8O3, Category: thiazolidine.

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

Huang, Yunjie published the artcileElexacaftor/tezacaftor/ivacaftor improved clinical outcomes in a patient with N1303K-CFTR based on in vitro experimental evidence, Synthetic Route of 307510-92-5, the publication is American Journal of Respiratory and Critical Care Medicine (2021), 204(10), 1231-1235, database is CAplus and MEDLINE.

Our study showed that treatment with ETI partially restored N1303K-CFTR expression and increased its function to nearly 40% of the wild-type level (Figure 1). Importantly, we have demonstrated clin. benefit of ETI in a child with N1303K (Figure 2), although the clin. response is slow and modest. Possibly, our patient’s second CFTR allele, E193X, and other genetic and nongenetic factors may contribute to this slow improvement as well.

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, Synthetic Route of 307510-92-5.

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

Deachapunya, Chatsri published the artcileActivation of Chloride Secretion by Isoflavone Genistein in Endometrial Epithelial Cells, Name: 4-((4-Oxo-2-thioxo-3-(3-(trifluoromethyl)phenyl)thiazolidin-5-ylidene)methyl)benzoic acid, the publication is Cellular Physiology and Biochemistry (2013), 32(5), 1473-1486, database is CAplus and MEDLINE.

Background /Aim: Genistein, the most active isoflavone found primarily in soybeans, alters ion transport functions in intestinal and airway epithelia. The present study aims to investigate the acute effects and mechanisms of action of genistein in immortalized porcine endometrial epithelial cells. Methods: Ussing chamber technique was used for transepithelial elec. measurements. Results: Genistein increased short-circuit currents (I_sc) which were inhibited by glibenclamide, NPPB, CFTRinh-172, DIDS or bumetanide, but not amiloride. In experiments with amphotericin B-permeabilized monolayers, genistein activated the apical Cl^– current and barium-sensitive basolateral K⁺ current while inhibiting the apical K⁺ current. Genistein failed to increase the I_sc in the presence of forskolin or IBMX, but did increase the I_sc in UTP. Pretreatment with genistein also abolished the increase in the I_sc when induced by forskolin, IBMX or UTP. However, Ca²⁺-chelating BAPTA-AM did not affect the genistein-induced increase in the I_sc. The genistein-stimulated I_sc was reduced by tyrosine kinase inhibitors, tyrphostin A23 or AG490. However, vanadate, a tyrosine phosphatase inhibitor, failed to inhibit the genistein response. Estrogen receptor antagonist ICI182,780 did not alter the genistein’s action. Conclusion: The soy isoflavone, genistein, stimulates Cl^– secretion in endometrial epithelial cells possibly via a direct activation of CFTR which appears to be modulated through a tyrosine kinase-dependent pathway. The present findings may be of benefit for the therapeutic application of genistein in the treatment of electrolyte transport disorders in the epithelia.

Cellular Physiology and 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 C18H10F3NO3S2, 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

Perniss, Alexander published the artcileHydrogen sulfide stimulates CFTR in Xenopus oocytes by activation of the cAMP/PKA signalling axis, Recommanded Product: 4-((4-Oxo-2-thioxo-3-(3-(trifluoromethyl)phenyl)thiazolidin-5-ylidene)methyl)benzoic acid, the publication is Scientific Reports (2017), 7(1), 1-11, database is CAplus and MEDLINE.

Hydrogen sulfide (H₂S) has been recognized as a signalling mol. which affects the activity of ion channels and transporters in epithelial cells. The cystic fibrosis transmembrane conductance regulator (CFTR) is an epithelial anion channel and a key regulator of electrolyte and fluid homeostasis. In this study, we investigated the regulation of CFTR by H₂S. Human CFTR was heterologously expressed in Xenopus oocytes and its activity was electrophysiol. measured by microelectrode recordings. The H₂S-forming sulfur salt Na₂S as well as the slow-releasing H₂S-liberating compound GYY4137 increased transmembrane currents of CFTR-expressing oocytes. Na₂S had no effect on native, non-injected oocytes. The effect of Na₂S was blocked by the CFTR inhibitor CFTR_inh172, the adenylyl cyclase inhibitor MDL 12330A, and the protein kinase A antagonist cAMPS-Rp. Na₂S potentiated CFTR stimulation by forskolin, but not that by IBMX. Na₂S enhanced CFTR stimulation by membrane-permeable 8Br-cAMP under inhibition of adenylyl cyclase-mediated cAMP production by MDL 12330A. These data indicate that H₂S activates CFTR in Xenopus oocytes by inhibiting phosphodiesterase activity and subsequent stimulation of CFTR by cAMP-dependent protein kinase A. In epithelia, an increased CFTR activity may correspond to a pro-secretory response to H₂S which may be endogenously produced by the epithelium or H₂S-generating microflora.

Scientific 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, 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

Wang, X. F. published the artcileEffects of a new cystic fibrosis transmembrane conductance regulator inhibitor on Cl^– conductance in human sweat ducts, COA of Formula: C18H10F3NO3S2, the publication is Experimental Physiology (2004), 89(4), 417-425, database is CAplus and MEDLINE.

Effective and specific inhibition of the cystic fibrosis transmembrane conductance regulator (CFTR) Cl^– channel in epithelia has long been needed to better understand the role of anion movements in fluid and electrolyte transport. Until now, available inhibitors have required high concentrations, usually in the millimolar or high micromolar range, to effect even an incomplete block of channel conductance. These inhibitors, including 5-nitro-2(3-phenylpropyl-amino)benzoate (NPPB), bumetamide, glibenclamide and DIDS, are also relatively non-specific. Recently a new anion channel inhibitor, a thiazolidinone derivative, termed CFTR_Inh-172 has been synthesized and introduced with apparently improved inhibitory properties as shown by effects on anion conductance expressed in cell lines and on secretion in vivo. Here, we assay the effect of this inhibitor on a purely salt absorbing native epithelial tissue, the freshly isolated microperfused human sweat duct, known for its inherently high expression of CFTR. We found that the inhibitor at a maximum dose limited by its aqueous solubility of 5 μm partially blocked CFTR when applied to either surface of the membrane; however, it may be somewhat more effective from the cytosolic side (∼70% inhibition). It may also partially inhibit Na⁺ conductance. The inhibition was relatively slow, with a half time for maximum effect of about 3 min, and showed very slow reversibility. Results also suggest that CFTR Cl^– conductance (G_Cl) was blocked in both apical and basal membranes. The inhibitor appears to exert some effect on Na⁺ transport as well.

Experimental 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 C12H10FeO4, COA of Formula: C18H10F3NO3S2.

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

Batista-Silva, Hemily published the artcileRole of bisphenol A on calcium influx and its potential toxicity on the testis of Danio rerio, Synthetic Route of 307510-92-5, the publication is Ecotoxicology and Environmental Safety (2020), 110876, database is CAplus and MEDLINE.

This study investigated the acute in vitro effect of low-concentration bisphenol A (BPA) on calcium (⁴⁵Ca²⁺) influx in zebrafish (Danio rerio) testis and examined whether intracellular Ca²⁺ was involved in the effects of BPA on testicular toxicity. In vitro studies on ⁴⁵Ca²⁺ influx were performed in the testes after incubation with BPA for 30 min. Inhibitors were added 15 min before the addition of ⁴⁵Ca²⁺ and BPA to testes to study the mechanism of action of BPA. The involvement of intracellular calcium from stores on lactate dehydrogenase (LDH) release and on triacylglycerol (TAG) content were carried out after in vitro incubation of testes with BPA for 1 h. Furthermore, gamma-glutamyl transpeptidase (GGT) and aspartate aminotransferase (AST) activities were analyzed in the liver at 1 h after in vitro BPA incubation of D. rerio. Our data show that the acute in vitro treatment of D. rerio testes with BPA at very low concentration activates plasma membrane ionic channels, such as voltage-dependent calcium channels and calcium-dependent chloride channels, and protein kinase C (PKC), which stimulates Ca²⁺ influx. In addition, BPA increased cytosolic Ca²⁺ by activating inositol triphosphate receptor (IP₃R) and inhibiting sarco/endoplasmic reticulum calcium ATPase (SERCA) at the endoplasmic reticulum, contributing to intracellular Ca²⁺ overload.

Ecotoxicology and Environmental Safety 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

Amato, Felice published the artcileTwo CFTR mutations within codon 970 differently impact on the chloride channel functionality, Recommanded Product: 4-((4-Oxo-2-thioxo-3-(3-(trifluoromethyl)phenyl)thiazolidin-5-ylidene)methyl)benzoic acid, the publication is Human Mutation (2019), 40(6), 742-748, database is CAplus and MEDLINE.

Pharmacol. rescue of mutant cystic fibrosis transmembrane conductance regulator (CFTR) in cystic fibrosis (CF) depends on the specific defect caused by different mutation classes. We asked whether a patient with the rare p.Gly970Asp (c.2909G>A) mutation could benefit from CFTR pharmacotherapy since a similar missense mutant p.Gly970Arg (c.2908G>C) was previously found to be sensitive to potentiators in vitro but not in vivo. By complementary DNA transfection, we found that both mutations are associated with defective CFTR function amenable to pharmacol. treatment. However, anal. of mRNA (mRNA) from patient’s cells revealed that c.2908G>C impairs RNA splicing whereas c.2909G>A does not perturb splicing and leads to the expected p.Gly970Asp mutation. In agreement with these results, nasal epithelial cells from the p.Gly970Asp patient showed significant improvement of CFTR function upon pharmacol. treatment. Our results underline the importance of controlling the effect of CF mutation at the mRNA level to determine if the pharmacotherapy of CFTR basic defect is appropriate.

Human Mutation 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

Morrison, Cameron B. published the artcileTreatment of cystic fibrosis airway cells with CFTR modulators reverses aberrant mucus properties via hydration, Product Details of C18H10F3NO3S2, the publication is European Respiratory Journal (2022), 59(2), 2100185, database is CAplus and MEDLINE.

Cystic fibrosis (CF) is characterised by the accumulation of viscous adherent mucus in the lungs. While several hypotheses invoke a direct relationship with cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction (i.e. acidic airway surface liquid (ASL) pH, low bicarbonate (HCO3-) concentration, airway dehydration), the dominant biochem. alteration of CF mucus remains unknown. We characterised a novel cell line (CFTR-KO Calu3 cells) and the responses of human bronchial epithelial (HBE) cells from subjects with G551D or F508del mutations to ivacaftor and elexacaftor-tezacaftor-ivacaftor. A spectrum of assays such as short-circuit currents, quant. PCR, ASL pH, Western blotting, light scattering/refractometry (size-exclusion chromatog. with inline multi-angle light scattering), SEM, percentage solids and particle tracking were performed to determine the impact of CFTR function on mucus properties. Loss of CFTR function in Calu3 cells resulted in ASL pH acidification and mucus hyperconcn. (dehydration). Modulation of CFTR in CF HBE cells did not affect ASL pH or mucin mRNA expression, but decreased mucus concentration, relaxed mucus network ultrastructure and improved mucus transport. In contrast with modulator-treated cells, a large fraction of airway mucins remained attached to naive CF cells following short apical washes, as revealed by the use of reducing agents to remove residual mucus from the cell surfaces. Extended hydration, but not buffers alkalised with sodium hydroxide or HCO3-, normalized mucus recovery to modulator-treated cell levels. These results indicate that airway dehydration, not acidic pH and/or low [HCO3-], is responsible for abnormal mucus properties in CF airways and CFTR modulation predominantly restores normal mucin entanglement.

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, Product Details of C18H10F3NO3S2.

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

Mu, Yong-hui published the artcileAlteration of mechanical stimulus-induced ions transport of distal colon in diarrhea predominant irritable bowel syndrome rat model, COA of Formula: C18H10F3NO3S2, the publication is Xinxiang Yixueyuan Xuebao (2014), 31(3), 166-169, database is CAplus.

It was investigated whether the mech. stimulus-induced ions transport of distal colon of rats with diarrhea predominant irritable bowel syndrome (D-IBS) was altered. The Sprague-Dawley rats were divided into control group and model group. The rats were exposed to individual housing combined with addnl. chronic unpredictable stress to induce D-IBS. The D-IBS model was tested by feces granules counting and sucrose consumption test. The mech. stimulus-induced ions transport of distal colon were investigated using short circuit current technique combined with removal extra-cellular anions and application of different blockers. The amount of feces granules was increased and sucrose consumption was decreased in model group compared with control group (P<0.05). There was no significant difference in electrophysiol. properties between control group and model group (P>0.05). The mech. stimulus-induced short-circuit current in model group was statistically higher than that in control group (P<0.05). The mech. stimulus-induced short-circuit current in both control group and model group were reduced significantly by removal of extracellular Cl^– (P<0.001) but not by HCO₃^–. The application of 4,4′-diisothiocyanato-stilbene-2,2′-disulfonic acid (DIDS), a Ca²⁺-activated Cl^– channel blocker, didn’t alter the short-circuit current induced by mech. stimulus in both groups. However, addition of CFTR (inh)-172, the inhibitor of cystic fibrosis transmembrane conductance regulator, or bumetanide, a blocker of Na⁺-K⁺-2Cl^– cotransproter reduced the mech. stimulus-induced short-circuit current in control group and model group significantly (P<0.001). The mech. stimulus could induce the secretion of Cl^– in distal colon of model rats, which was a possible mechanism responsible for the diarrhea of D-IBS rats.

Xinxiang Yixueyuan Xuebao 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