Category: 59973-80-7

Yoon, Jung-Taek published the artcileCP248, a derivative of exisulind, causes growth inhibition, mitotic arrest, and abnormalities in microtubule polymerization in glioma cells, Category: naphthyridine, the publication is Molecular Cancer Therapeutics (2002), 1(6), 393-404, database is CAplus and MEDLINE.

Exisulind (sulindac sulfone) and two potent derivatives, CP248 and CP461, have been shown previously to cause growth inhibition and apoptosis in several types of human carcinoma cell lines. These and related compounds have not been previously studied with respect to glioma cell lines. In the present study, we found that these three compounds caused marked growth inhibition in four rat glioma and eight human glioma cell lines, with IC₅₀ values of 150, 1, and 0.075 μM, resp. When studied at these concentrations exisulind and CP461 had no significant effect on the cell cycle profile of glioma cells, but CP248 caused marked arrest in mitosis. Detailed studies of CP248 in the 9L rat gliosarcoma cell line indicated that treatment with 0.075 μM CP248 caused abnormalities in the spindle apparatus and activation of the spindle assembly check point. In interphase glioma cells, CP248 stabilized microtubules (MTs) at low concentrations (0.075 μM) and depolymerized MTs at higher concentrations (0.2-0.4 μM). In NIH 3T3 fibroblasts, 0.1 μM CP248 caused extensive MT depolymerization CP248 also caused MT depolymerization when added to assembled MTs in vitro, which indicated that it can directly affect MTs, perhaps because it shares certain structural similarities with Colcemid. In glioma cells, the effects of CP248 on MTs were independent of the previously reported effects of this compound on activation of protein kinase G. Therefore, CP248 is a novel MT-active agent that may be useful in the treatment of glioblastoma, and possibly other types of cancer, because of its dual effects on protein kinase G and MTs.

Molecular Cancer Therapeutics published new progress about 59973-80-7. 59973-80-7 belongs to naphthyridine, auxiliary class Immunology/Inflammation,COX, name is Sulindac sulfone, and the molecular formula is C9H8BNO2, Category: naphthyridine.

Referemce:
https://en.wikipedia.org/wiki/1,8-Naphthyridine,
1,8-Naphthyridine | C8H6N2 – PubChem

Lee, Jin Kyung published the artcileSulindac and its metabolites inhibit multiple transport proteins in rat and human hepatocytes, Recommanded Product: Sulindac sulfone, the publication is Journal of Pharmacology and Experimental Therapeutics (2010), 334(2), 410-418, database is CAplus and MEDLINE.

Sulindac is a commonly used nonsteroidal anti-inflammatory drug. This study tested the hypothesis that sulindac-mediated drug-drug interactions and/or hepatotoxicity may be caused, in part, by inhibition of proteins responsible for the hepatic transport of drugs and/or bile acids by sulindac and/or sulindac metabolites [sulindac sulfone (S-sulfone) and sulindac sulfide (S-sulfide)]. The uptake and excretion of model substrates, [³H]taurocholate (TC), [³H]estradiol 17-β-glucuronide (E217G), and nitrofurantoin (NF), were investigated in rat and human suspended and sandwich-cultured hepatocytes (SCH). In suspended rat hepatocytes, S-sulfone and S-sulfide inhibited Na⁺-dependent TC initial uptake (IC₅₀ of 24.9 ± 6.4 and 12.5 ± 1.8 μM, resp.) and Na⁺-independent E217G initial uptake (IC₅₀ of 12.1 ± 1.6 and 6.3 ± 0.3 μM, resp.). In rat SCH, sulindac metabolites (100 μM) decreased the in vitro biliary clearance (Cl_biliary) of TC, E217G, and NF by 38 to 83%, 81 to 97%, and 33 to 57%, resp.; S-sulfone and S-sulfide also decreased the TC and NF biliary excretion index by 39 to 55%. In suspended human hepatocytes, S-sulfone and S-sulfide inhibited Na⁺-dependent TC initial uptake (IC₅₀ of 42.2 and 3.1 μM, resp.); S-sulfide also inhibited the TC Cl_biliary in human SCH. Sulindac/metabolites markedly inhibited hepatic uptake and biliary excretion of E217G by 51 to 100% in human SCH. In conclusion, sulindac and metabolites are potent inhibitors of the uptake and biliary clearance of bile acids in rat and human hepatocytes and also inhibit substrates of rat breast cancer resistance protein, rat and human organic anion-transporting polypeptides, and human multidrug resistance-associated protein 2. Inhibition of multiple hepatic transport proteins by sulindac/metabolites may play an important role in clin. significant sulindac-mediated drug-drug interactions and/or liver injury.

Journal of Pharmacology and Experimental Therapeutics published new progress about 59973-80-7. 59973-80-7 belongs to naphthyridine, auxiliary class Immunology/Inflammation,COX, name is Sulindac sulfone, and the molecular formula is C20H17FO4S, Recommanded Product: Sulindac sulfone.

Referemce:
https://en.wikipedia.org/wiki/1,8-Naphthyridine,
1,8-Naphthyridine | C8H6N2 – PubChem

Li, Han published the artcileβ-Catenin signaling: therapeutic strategies in oncology, COA of Formula: C20H17FO4S, the publication is Cancer Biology & Therapy (2002), 1(6), 621-625, database is CAplus and MEDLINE.

A review. Activated Wnt signaling pathways have been found in various human cancers, including those of the colon, liver, endometrium, ovary, prostate, and stomach. As a result, β-catenin is accumulated and becomes transcriptionally active for proliferative genes and oncogenes. Wnt pathway mutations result in biochem. mechanisms yielding inefficient phosphorylation of β-catenin by glycogen synthase kinase 3β (GSK3β) due to APC, β-catenin and/or axin mutations. Therefore, the needs and the opportunity to develop new cancer therapies exist through reversing oncogenic APC/β-catenin/Lef/Tcf signals. Exisulind and analogs are inhibitors of cyclic GMP phosphodiesterases (PDE) that have been shown to activate and induce protein kinase G. The data show PKG regulation of β-catenin in Wnt signaling, accounting, at least in part, for apoptosis induction in treated colon cancer cells carrying either APC or β-catenin mutations. Exisulind and analogs reduce β-catenin via a novel, GSK3β independent processing mechanism. Activated PKG directly phosphorylate β-catenin at its C-terminal domain and causes proteasome dependent degradation of the protein. Since this pathway is independent of APC and GSK3β, exisulind and analogs provide a superior approach to circumvent the mol. defects of Wnt signaling pathway and to treat cancers with such defects.

Cancer Biology & Therapy published new progress about 59973-80-7. 59973-80-7 belongs to naphthyridine, auxiliary class Immunology/Inflammation,COX, name is Sulindac sulfone, and the molecular formula is C20H17FO4S, COA of Formula: C20H17FO4S.

Referemce:
https://en.wikipedia.org/wiki/1,8-Naphthyridine,
1,8-Naphthyridine | C8H6N2 – PubChem

Pitari, Giovanni Mario published the artcileExisulind and guanylyl cyclase C induce distinct antineoplastic signaling mechanisms in human colon cancer cells, SDS of cas: 59973-80-7, the publication is Molecular Cancer Therapeutics (2006), 5(5), 1190-1196, database is CAplus and MEDLINE.

The nonsteroidal anti-inflammatory drug sulindac is metabolized to sulindac sulfone (exisulind), an antineoplastic agent that inhibits growth and induces apoptosis in solid tumors. In colon cancer cells, the antineoplastic effects of exisulind have been attributed, in part, to induction of cyclic guanosine 3′,5′-monophosphate (cGMP) signaling through inhibition of cGMP-specific phosphodiesterases, which elevates intracellular cGMP, and novel expression of cGMP-dependent protein kinase (PKG) Iβ, the presumed downstream effector mediating apoptosis. Here, inhibition of proliferation and induction of cell death by exisulind was dissociated from cGMP signaling in human colon cancer cells. Accumulation of intracellular cGMP produced by an exogenous cell-permeant analog of cGMP or a potent agonist of guanylyl cyclase C yielded cytostasis without cell death. Surprisingly, the antiproliferative effects of induced cGMP accumulation were paradoxically less than additive, rather than synergistic, when combined with exisulind. Further, although exisulind induced expression of PKG Iβ, it did not elevate intracellular cGMP and its efficacy was not altered by inhibition or activation of PKG I. Rather, PKG I induced by exisulind may mediate desensitization of cytostasis induced by cGMP. Thus, cytotoxic effects of exisulind are independent of cGMP signaling in human colon cancer cells. Moreover, combination therapies, including exisulind and agents that induce cGMP signaling, may require careful evaluation in patients with colon cancer.

Molecular Cancer Therapeutics published new progress about 59973-80-7. 59973-80-7 belongs to naphthyridine, auxiliary class Immunology/Inflammation,COX, name is Sulindac sulfone, and the molecular formula is C20H17FO4S, SDS of cas: 59973-80-7.

Referemce:
https://en.wikipedia.org/wiki/1,8-Naphthyridine,
1,8-Naphthyridine | C8H6N2 – PubChem

Zhong, Min published the artcileCarcinogenicity Prediction of Noncongeneric Chemicals by a Support Vector Machine, Application In Synthesis of 59973-80-7, the publication is Chemical Research in Toxicology (2013), 26(5), 741-749, database is CAplus and MEDLINE.

The ability to identify carcinogenic compounds is of fundamental importance to the safe application of chems. In this study, the authors generated an array of in silico models allowing the classification of compounds into carcinogenic and noncarcinogenic agents based on a data set of 852 noncongeneric chems. collected from the Carcinogenic Potency Database (CPDBAS). Twenty-four mol. descriptors were selected by Pearson correlation, F-score, and stepwise regression anal. These descriptors cover a range of physicochem. properties, including electrophilicity, geometry, mol. weight, size, and solubility The descriptor mutagenic showed the highest correlation coefficient with carcinogenicity. On the basis of these descriptors, a support vector machine-based (SVM) classification model was developed and fine-tuned by a 10-fold cross-validation approach. Both the SVM model (Model A1) and the best model from the 10-fold cross-validation (Model B3) runs gave good results on the test set with prediction accuracy over 80%, sensitivity over 76%, and specificity over 82%. In addition, extended connectivity fingerprints (ECFPs) and the Toxtree software were used to analyze the functional groups and substructures linked to carcinogenicity. It was found that the results of both methods are in good agreement.

Chemical Research in Toxicology published new progress about 59973-80-7. 59973-80-7 belongs to naphthyridine, auxiliary class Immunology/Inflammation,COX, name is Sulindac sulfone, and the molecular formula is C10H16Br3N, Application In Synthesis of 59973-80-7.

Referemce:
https://en.wikipedia.org/wiki/1,8-Naphthyridine,
1,8-Naphthyridine | C8H6N2 – PubChem

Narayanan, Bhagavathi A. published the artcileRegression of mouse prostatic intraepithelial neoplasia by nonsteroidal anti-inflammatory drugs in the transgenic adenocarcinoma mouse prostate model, Name: Sulindac sulfone, the publication is Clinical Cancer Research (2004), 10(22), 7727-7737, database is CAplus and MEDLINE.

Epidemiol. studies have revealed a decreased risk of colon cancer among people who have regularly taken cyclooxygenase (COX)-2 inhibitors such as aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs). Whereas the selective COX-2 inhibitor celecoxib and exisulind, a metabolic product of sulindac, have gained increasing attention as efficacious chemopreventive agents against colon and prostate cancer, not much is known about the underlying mol. targets and mechanisms. Moreover, the side effects of NSAIDs are a major obstacle for large-scale application to the prevention of cancer in humans; for example, in the United States in 1998, there were 16,550 deaths from NSAID-induced gastrointestinal complications. The toxicity associated with these compounds is raising concerns, and more needs to be known about their mode of action and mol. targets. We used the transgenic mouse prostate (TRAMP) model, which exhibits similarities with human prostate cancer, including epithelial origin, progression from the PIN stage to adenocarcinoma, and metastasis by a transgene that is hormonally regulated by androgens. In addition to histol. analyzing the PIN lesions of the dorsolateral prostate from TRAMP mice, we delineated the mol. targets and mechanisms of celecoxib and exisulind against mouse PIN lesions. We performed Western blot anal. of the total protein lysate from the tissues of mouse PIN lesions to measure the level of expression of androgen receptor, vascular endothelial growth factor, nuclear factor-κB p65, BclII, AKT (total and phosphorylated Ser⁴⁷³), p53, cyclin-dependent kinase inhibitor p21^WAF1/CIP1, p27, BAX, and caspase-3 to demonstrate the COX-2-independent mechanism involved in the inhibition of PIN lesions of the dorsolateral prostate by both celecoxib and exisulind. We found for the first time that (a) both celecoxib and exisulind as dietary supplements induce strong inhibitory effects against prostate cancer at doses of 800 and 500 ppm, resp., after 16 wk; (b) the histol. anal. of the dorsolateral prostate after 2 wk of treatment indicated a reduction of PIN lesions from 75% to 19% with celecoxib and to 16% with exisulind; (c) more importantly, those few PINs and adenocarcinomas in the groups treated with celecoxib or exisulind showed more apoptotic cells, lower levels of proliferating cell nuclear antigen, and a lower number of mitotic cells. To understand the mol. mechanisms involved in the inhibition of PIN lesions, first, we examined the expression of mol. targets involved in angiogenesis and inflammatory processes. It was clearly evident from Western blot anal. of the total protein lysate derived from the dorsolateral prostate tissues with PIN lesions that expression of androgen receptor, vascular endothelial growth factor, nuclear factor-κB p65, and BclII is down-regulated more effectively by celecoxib. Down-regulation of AKT protein (total and phosphorylated at Ser⁴⁷³) signaling by celecoxib clearly indicates an inhibition of the survival gene and the pathol. process that could otherwise lead to adenocarcinoma. Overall, the findings from this study clearly show the effectiveness of celecoxib and exisulind in reducing the PIN lesions by modulating a cascade of mol. targets involved in COX-2-dependent and -independent mechanisms. Whereas these agents are already in clin. trial or in use as chemopreventive agents, findings from this study demonstrate the difference in their mode of action, thus helping us to understand the side effects.

Clinical Cancer Research published new progress about 59973-80-7. 59973-80-7 belongs to naphthyridine, auxiliary class Immunology/Inflammation,COX, name is Sulindac sulfone, and the molecular formula is C20H17FO4S, Name: Sulindac sulfone.

Referemce:
https://en.wikipedia.org/wiki/1,8-Naphthyridine,
1,8-Naphthyridine | C8H6N2 – PubChem

Mashal, Mohammad Shafiq published the artcileSimultaneous quantification of 19 nonsteroidal anti-inflammatory drugs in oral fluid by liquid chromatography-high resolution mass spectrometry: Application on ultratrail runners oral fluid, HPLC of Formula: 59973-80-7, the publication is Drug Testing and Analysis (2022), 14(4), 701-712, database is CAplus and MEDLINE.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are a therapeutic class suspected to be used by ultratrail runners. The use of NSAIDs during ultratrails is known to be associated with various adverse effects. To study the prevalence of NSAIDs intake in ultratrail runners, oral fluid (OF) is a relevant matrix as it is noninvasive and easy to collect. The aim of our work was to develop and validate a liquid-liquid extraction followed by a liquid chromatog. (LC)-mass spectrometry (MS)/high resolution mass spectrometry (HRMS) method for the simultaneous quantification of 19 NSAIDs in OF. After a comparison of different liquid-liquid extraction methods, a double step liquid-liquid extraction with chloroform was performed on OF collected with Quantisal, with extraction recoveries higher than 90%. An Accucore AQ column was selected for the chromatog. separation of NSAIDs. The Q Exactive Plus mass spectrometer operated in full scan and ddms2 mode after pos. and neg. electrospray ionization. Selectivity, carry-over, matrix effect, and linearity were validated for all NSAIDs. Within-day and between-day accuracy and precision were validated for all NSAIDs (<15% for quality control [QC] samples and <20% for lower limit of quantitation [LLOQ]), except within-day accuracy for the LLOQ of mefenamic acid. A stability study was also performed on OF at room temperature and +4°C. The method was applied on OF from runners who participate to Ultra Trail du Mont Blanc.

Drug Testing and Analysis published new progress about 59973-80-7. 59973-80-7 belongs to naphthyridine, auxiliary class Immunology/Inflammation,COX, name is Sulindac sulfone, and the molecular formula is C20H17FO4S, HPLC of Formula: 59973-80-7.

Referemce:
https://en.wikipedia.org/wiki/1,8-Naphthyridine,
1,8-Naphthyridine | C8H6N2 – PubChem

Isojima, Yasushi published the artcileCkIε/δ-dependent phosphorylation is a temperature-insensitive, period-determining process in the mammalian circadian clock, Formula: C20H17FO4S, the publication is Proceedings of the National Academy of Sciences of the United States of America (2009), 106(37), 15744-15749, S15744/1-S15744/74, database is CAplus and MEDLINE.

A striking feature of the circadian clock is its flexible yet robust response to various environmental conditions. To analyze the biochem. processes underlying this flexible-yet-robust characteristic, we examined the effects of 1260 pharmacol. active compounds in mouse and human clock cell lines. Compounds that markedly (>10 s.d.) lengthened the period in both cell lines, also lengthened it in-central clock tissues and peripheral clock cells. Most compounds inhibited casein kinase Iε (CKIε) or CKIδ phosphorylation of the PER2 protein. Manipulation of CKIε/δ-dependent phosphorylation by these compounds lengthened the period of the mammalian clock from circadian (24 h) to circabidian (48 h), revealing its high sensitivity to chem. perturbation. The degradation rate of PER2, which is regulated by CKIε/δ-dependent phosphorylation, was temperature-insensitive in living clock cells, yet sensitive to chem. perturbations. This temperature-insensitivity was preserved in the CKIε/δ-dependent phosphorylation of a synthetic peptide in vitro. Thus, CKIε/δ-dependent phosphorylation is likely a temperature-insensitive period-determining process in the mammalian circadian clock.

Proceedings of the National Academy of Sciences of the United States of America published new progress about 59973-80-7. 59973-80-7 belongs to naphthyridine, auxiliary class Immunology/Inflammation,COX, name is Sulindac sulfone, and the molecular formula is C20H17FO4S, Formula: C20H17FO4S.

Referemce:
https://en.wikipedia.org/wiki/1,8-Naphthyridine,
1,8-Naphthyridine | C8H6N2 – PubChem

Shirin, Haim published the artcileNon-steroidal anti-inflammatory drugs have bacteriostatic and bactericidal activity against Helicobacter pylori, Category: naphthyridine, the publication is Journal of Gastroenterology and Hepatology (2006), 21(9), 1388-1393, database is CAplus and MEDLINE.

Helicobacter pylori infection and non-steroidal anti-inflammatory drugs (NSAIDs) are each associated with gastrointestinal mucosal damage, but the extent and direction of their interactions remain controversial. Therefore, the purpose of the present paper was to examine whether specific NSAIDs inhibit the growth of Helicobacter pylori in vitro. Sodium salicylate, ibuprofen, indomethacin, the selective cyclooxygenase-2 inhibitor NS-398 and two derivatives of sulindac sulfoxide were tested against two laboratory strains of H. pylori, the mouse-adapted Sydney strain, and against seven fresh clin. isolates of Helicobacter pylori. Possible effects on Campylobacter jejuni, Staphyloccoccus aureus, Escherichia coli, Salmonella typhimurium, and Shigella boydii were also examined Certain NSAIDs possess antibacterial activity against Helicobacter pylori at therapeutically achievable doses; an effect that appears to be independent of cyclooxygenase enzymes inhibition. For Helicobacter pylori, >90% growth inhibition and bactericidal activity were observed consistently for sulindac sulfide at â‰?0 μg/mL and sulindac sulfone at â‰?75 μg/mL. The minimal inhibitory concentration against Helicobacter pylori was 125 μg/mL for ibuprofen, 100 μg/mL for indomethacin and 300 μg/mL for NS-398 but much higher concentration of sodium salicylate (4000 μg/mL) and sulindac sulfoxide (â‰?250 μg/mL) were required to inhibit the growth of Helicobacter pylori. The decreased prevalence of Helicobacter pylori in specimens from some NSAID users and the chemopreventive effects of NSAIDs in gastric cancer may be related to inhibition of Helicobacter pylori growth.

Journal of Gastroenterology and Hepatology published new progress about 59973-80-7. 59973-80-7 belongs to naphthyridine, auxiliary class Immunology/Inflammation,COX, name is Sulindac sulfone, and the molecular formula is C4H6O3, Category: naphthyridine.

Referemce:
https://en.wikipedia.org/wiki/1,8-Naphthyridine,
1,8-Naphthyridine | C8H6N2 – PubChem

Stock, Nicholas published the artcileThe geminal dimethyl analogue of Flurbiprofen as a novel Aβ₄₂ inhibitor and potential Alzheimer’s disease modifying agent, Recommanded Product: Sulindac sulfone, the publication is Bioorganic & Medicinal Chemistry Letters (2006), 16(8), 2219-2223, database is CAplus and MEDLINE.

The subtle modification of a selection of Aβ₄₂ inhibiting non-steroidal anti-inflammatory drugs (NSAIDs), through synthesis of the geminal di-Me analogs, was anticipated to ablate their cyclooxygenase activity while maintaining Aβ₄₂ inhibition. Methylflurbiprofen I exhibited similar in vitro Aβ₄₂ inhibition to its parent NSAID Flurbiprofen and was further evaluated in the Tg2576 mouse model of Alzheimer’s disease and an animal model of gastro-intestinal (GI) impairment, but proved unviable for further clin. development.

Bioorganic & Medicinal Chemistry Letters published new progress about 59973-80-7. 59973-80-7 belongs to naphthyridine, auxiliary class Immunology/Inflammation,COX, name is Sulindac sulfone, and the molecular formula is C16H10O5, Recommanded Product: Sulindac sulfone.

Referemce:
https://en.wikipedia.org/wiki/1,8-Naphthyridine,
1,8-Naphthyridine | C8H6N2 – PubChem