Tag: M.W=400-450

He, Cheng-yan published the artcileSynthesis and characterization of a small molecule CFTR chloride channel inhibitor, Category: thiazolidine, the publication is Chemical Research in Chinese Universities (2004), 20(3), 334-337, database is CAplus.

A thiazolidinone CFTR inhibitor (CFTR_inh-172) was synthesized by a three-step procedure with trifluoromethylaniline as the starting material. The synthesized CFTR inhibitor was characterized structurally by ¹H-NMR and functionally in a CFTR-expressing cell line FRT/hCFTR/EYFP-H148Q by both fluorescent and electrophysiol. methods. A large amount (100 g) of high-quality small mol. thiazolidinone CFTR chloride channel inhibitor, CFTR_inh-172, can be produced with this simple three-step synthetic procedure. The structure of the final product 2-thioxo-3-(3-trifluoromethylphenyl)-5-[4-carboxyphenyl-methylene]-4-thiazolidinone was confirmed by ¹H NMR. The overall yield was 58% with a purity over 99% as analyzed by HPLC. The synthesized CFTR_inh-172 specifically inhibited CFTR chloride channel function in a cell-based fluorescence assay (K_d≈1.5 μmol/L) and in a Ussing chamber-based short-circuit current assay (K_d≈0.2 μmol/L), indicating better quality than that of the com. combinatorial compound The synthesized inhibitor is nontoxic to cultured cells at a high concentration and to mouse at a high dose. The synthetic procedure developed here can be used to produce a large amount of the high-quality CFTR_inh-172 suitable for antidiarrheal studies and for creation of cystic fibrosis models in large animals. The procedure can be used to synthesize radiolabeled CFTR_inh-172 for in vivo pharmacokinetics studies.

Chemical Research in Chinese Universities 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

Nick, Heidi J. published the artcileMeasurements of spontaneous CFTR-mediated ion transport without acute channel activation in airway epithelial cultures after modulator exposure, Formula: C18H10F3NO3S2, the publication is Scientific Reports (2021), 11(1), 22616, database is CAplus and MEDLINE.

Quantitation of CFTR function in vitro is commonly performed by acutely stimulating then inhibiting ion transport through CFTR and measuring the resulting changes in transepithelial voltage (V_te) and current (I_SC). While this technique is suitable for measuring the maximum functional capacity of CFTR, it may not provide an accurate estimate of in vivo CFTR activity. To test if CFTR-mediated ion transport could be measured in the absence of acute CFTR stimulation, primary airway epithelia were analyzed in an Ussing chamber with treatment of amiloride followed by CFTR(inh)-172 without acute activation of CFTR. Non-CF epithelia demonstrated a decrease in V_te and I_SC following exposure to CFTR(inh)-172 and in the absence of forskolin/IBMX (F/I); this decrease is interpreted as a measure of spontaneous CFTR activity present in these epithelia. In F508del/F508del CFTR epithelia, F/I-induced changes in V_te and I_SC were ∼ fourfold increased after treatment with VX-809/VX-770, while the magnitude of spontaneous CFTR activities were only ∼ 1.6-fold increased after VX-809/VX-770 treatment. Method-dependent discrepancies in the responses of other CF epithelia to modulator treatments were observed These results serve as a proof of concept for the anal. of CFTR modulator responses in vitro in the absence of acute CFTR activation. Future studies will determine the usefulness of this approach in the development of novel CFTR modulator therapies.

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, Formula: C18H10F3NO3S2.

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

Leir, Shih-Hsing published the artcileAn organoid model to assay the role of CFTR in the human epididymis epithelium, SDS of cas: 307510-92-5, the publication is Cell & Tissue Research (2020), 381(2), 327-336, database is CAplus and MEDLINE.

Abstract: Organoid cultures derived from primary human tissues facilitate the study of disease processes and the development of new therapeutics. We used human epididymis epithelial cell (HEE) organoids and polarized HEE cell cultures to assay the CF transmembrane conductance regulator (CFTR) in the human epididymis. 3D HEE organoids and polarized 2D HEE cell cultures on membrane inserts were established from human caput epididymis. Single-cell RNA sequencing (scRNA-seq) was performed to map cell type-specific gene expression in the organoids. Using forskolin (FSK) to activate CFTR and inhibitor CFTRinh₁₇₂ to block its activity, we assessed how CFTR contributes to organoid swelling and epithelial barrier function. The scRNA-seq data showed key caput epididymis cell types present in HEE organoid cultures. FSK at 10 μM induced HEE organoid swelling by 20% at 16 h, while 5 and 10 μM CFTRinh₁₇₂ treatment significantly reduced HEE organoid size. FSK treatment significantly increased the flux of 4-kDa but not 70-kDa dextran, suggesting activation of CFTR mainly enhances transcellular diffusion. We have demonstrated that CFTR contributes to the maintenance of HEE cell TER and that cultured HEE organoids are a useful model to investigate human epididymis function. These results facilitate progress in elucidating how CFTR-dependent cellular processes impair fertility in CF.

Cell & Tissue 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, SDS of cas: 307510-92-5.

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

Xu, Qianqian published the artcileApplication progress in CFTR inhibitors in the treatment of secretory diarrhea, Safety of 4-((4-Oxo-2-thioxo-3-(3-(trifluoromethyl)phenyl)thiazolidin-5-ylidene)methyl)benzoic acid, the publication is Zhongguo Yaoshi (Wuhan, China) (2015), 18(8), 1378-1382, database is CAplus.

A review. Secretory diarrhea provided a major health challenge worldwide which was one of the most important reasons for children morbidity and death. The activation of Cl^– channels in intestinal epithelial cells resulting in the excessive fluid secretion in the intestine was the main reason of diarrhea caused by enterotoxins. In diarrhea caused by cholera and the other bacterial enterotoxins, cystic fibrosis transmembrane conductance regulator (CFTR) was the main cAMP-control Cl^– channel to promote the fluid secretion in epithelial cells. Therefore, CFTR inhibitors were the new choices for secretory diarrhea. CFTR inhibitors included thiazolidinone, glycine hydrazide and quinoxalinedione chem. classes, and some components from natural plants also exhibited CFTR inhibition activity, however, further studies should be done.

Zhongguo Yaoshi (Wuhan, China) 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 C9H17NO, 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

Tian, Sheng published the artcileDrug-likeness Analysis of Traditional Chinese Medicines: Prediction of Drug-likeness Using Machine Learning Approaches, Application of 4-((4-Oxo-2-thioxo-3-(3-(trifluoromethyl)phenyl)thiazolidin-5-ylidene)methyl)benzoic acid, the publication is Molecular Pharmaceutics (2012), 9(10), 2875-2886, database is CAplus and MEDLINE.

Quant. or qual. characterization of the drug-like features of known drugs may help medicinal and computational chemists to select higher quality drug leads from a huge pool of compounds and to improve the efficiency of drug design pipelines. For this purpose, the theor. models for drug-likeness to discriminate between drug-like and non-drug-like based on mol. physicochem. properties and structural fingerprints were developed by using the naive Bayesian classification (NBC) and recursive partitioning (RP) techniques, and then the drug-likeness of the compounds from the Traditional Chinese Medicine Compound Database (TCMCD) was evaluated. First, the impact of mol. physicochem. properties and structural fingerprints on the prediction accuracy of drug-likeness was examined We found that, compared with simple mol. properties, structural fingerprints were more essential for the accurate prediction of drug-likeness. Then, a variety of Bayesian classifiers were constructed by changing the ratio of drug-like to non-drug-like mols. and the size of the training set. The results indicate that the prediction accuracy of the Bayesian classifiers was closely related to the size and the degree of the balance of the training set. When a balanced training set was used, the best Bayesian classifier based on 21 physicochem. properties and the LCFP_6 fingerprint set yielded an overall leave-one-out (LOO) cross-validated accuracy of 91.4% for the 140,000 mols. in the training set and 90.9% for the 40,000 mols. in the test set. In addition, the RP classifiers with different maximum depth were constructed and compared with the Bayesian classifiers, and we found that the best Bayesian classifier outperformed the best RP model with respect to overall prediction accuracy. Moreover, the Bayesian classifier employing structural fingerprints highlights the important substructures favorable or unfavorable for drug-likeness, offering extra valuable information for getting high quality lead compounds in the early stage of the drug design/discovery process. Finally, the best Bayesian classifier was used to predict the drug-likeness of 33,961 compounds in TCMCD. Our calculations show that 59.37% of the mols. in TCMCD were identified as drug-like mols., indicating that traditional Chinese medicines (TCMs) are therefore an excellent source of drug-like mols. Furthermore, the important structural fingerprints in TCMCD were detected and analyzed. Considering that the pharmacol. of TCMCD and MDDR (MDL Drug Data Report) was linked by the important common structural features, the potential pharmacol. of the compounds in TCMCD may therefore be annotated by these important structural signatures identified from Bayesian anal., which may be valuable to promote the development of TCMs.

Molecular Pharmaceutics 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 C8H6ClN, Application 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

Begrow, Frank published the artcileEffect of Ap4A, UTP and Salbutamol on mucociliary clearance in a mouse model of cystic fibrosis (in situ), HPLC of Formula: 307510-92-5, the publication is Pharmacology & Pharmacy (2013), 4(2), 176-181, 6 pp., database is CAplus.

Cystic fibrosis is a life-threatening, wide spread genetic disease diagnosed in 1 to 3000 live births of the Caucasian population. Here a mouse model for this disease is described and optimized using the CFTR-channel selective inhibitor CFTR(inh 172). The target parameter was mucociliary clearance measured using microdialysis of the transported fluorescent dye rhodamine in the mouse trachea in situ. The impact of Ap4A (diadenosine tetraphosphate) as a potential drug was investigated. Its inhalation was effective at low concentrations; established compounds such as Salbutamol and UTP increased mucociliary clearance as well. Our data show a functioning model of cystic fibrosis and the effectiveness of the newly tested Ap4A.

Pharmacology & Pharmacy 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, HPLC of Formula: 307510-92-5.

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

Buyck, J. M. published the artcileP. aeruginosa LPS stimulates calcium signaling and chloride secretion via CFTR in human bronchial epithelial cells, Category: thiazolidine, the publication is Journal of Cystic Fibrosis (2013), 12(1), 60-67, database is CAplus and MEDLINE.

Background: Pseudomonas aeruginosa airway infection is associated with a high mortality rate in cystic fibrosis. Lipopolysaccharide (LPS), a main constituent of the outer membrane of P. aeruginosa, is responsible for activation of innate immune response but its role on airway epithelium ion transport, is not well known. The aim of this study was to determine the role for P. aeruginosa LPS in modulating chloride secretion and intracellular calcium in the human bronchial epithelial cell line, 16HBE14o -. Methods: We used intracellular calcium imaging and short-circuit current measurement upon exposure of cells to P. aeruginosa LPS. Results: Apical LPS stimulated intracellular calcium release and calcium entry and enhanced chloride secretion. This latter effect was significantly inhibited by CFTR(inh)-172 and BAPTA-AM (intracellular Ca^2 + chelator). Conclusions: Our data provides evidence for a new role of P. aeruginosa LPS in stimulating calcium entry and release and a subsequent chloride secretion via CFTR in human bronchial epithelium.

Journal of Cystic Fibrosis 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

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

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

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