Category: 59973-80-7

Kuehl, Gwendolyn E. published the artcileGlucuronidation of nonsteroidal anti-inflammatory drugs: Identifying the enzymes responsible in human liver microsomes, Application In Synthesis of 59973-80-7, the publication is Drug Metabolism and Disposition (2005), 33(7), 1027-1035, database is CAplus and MEDLINE.

Nonsteroidal anti-inflammatory drugs (NSAIDs), used for the treatment of pain and inflammation, are eliminated primarily through conjugation with polar sugar moieties to form glucuronides. Glucuronidation is catalyzed by the UDP-glucuronosyltransferases (UGT) superfamily. An inverse relationship may exist between glucuronidation activity and NSAID efficacy; however, specific UGTs catalyzing conjugation of the structurally diverse NSAIDs have yet to be identified systematically. Therefore, NSAID glucuronidation activity by 12 individually expressed UGTs was investigated by liquid chromatog.-tandem mass spectrometry. The relative rates of NSAID glucuronidation varied among UGT enzymes examined, demonstrating specificity of the individual UGTs toward selected NSAIDs. Kinetic parameters were determined for expressed UGT Supersomes and compared with parameters determined in pooled human liver microsomes (HLMs). Comparison of K_m values suggested roles for UGTs 1A3 and 2B7 in indene glucuronidation and UGTs 1A9, 2B4, and 2B7 in profen glucuronidation. Inhibitory studies in pooled HLMs support the role of UGTs 1A1, 1A3, 1A9, 2B4, and 2B7 in the glucuronidation of ibuprofen, flurbiprofen, and ketoprofen. Bilirubin did not inhibit indomethacin or diclofenac glucuronidation, suggesting that UGT1A1 was not involved in catalysis. Imipramine did not inhibit glucuronidation of sulindac, sulindac sulfone, indomethacin, or naproxen in pooled HLMs, suggesting that UGT1A3 was not a principal hepatic catalyst. Nevertheless, multiple UGT enzymes, most notably UGTs 1A1, 1A9, 2B4, and 2B7, seem to be involved in the hepatic catalysis of NSAID glucuronidation.

Drug Metabolism and Disposition 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, Application In Synthesis of 59973-80-7.

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

Kwak, Min Seob published the artcileNovel candidate drugs in anti-tumor necrosis factor refractory Crohn’s diseases: in silico study for drug repositioning, Recommanded Product: Sulindac sulfone, the publication is Scientific Reports (2020), 10(1), 10708, database is CAplus and MEDLINE.

Abstract: Biologicals like anti-tumor necrosis factor (TNF) therapy for Crohn’s disease (CD) are safe and effective but there is a significant rate of primary and secondary nonresponse in the patients. In this study, we applied a computational approach to discover novel drug therapies for anti-TNF refractory CD in silico. We use a transcriptome dataset (GSE100833) for the anti-TNF refractory CD patients from NCBI GEO. After co-expression anal., we specifically investigated the extent of protein-protein interactions among genes in clusters based on a protein-protein interaction database, STRING. Pathway anal. was performed using the clEnrich function based on KEGG gene sets. Co-expressed genes in cluster 1, 2, 3, 4, up or down-regulated genes and all differentially expressed genes are highly connected. Among them, cluster 1, which is highly enriched for chemokine signaling, also showed enrichment for cytokine-cytokine receptor interaction and identifies several drugs including cyclosporin with known efficacy in CD. Vorinostat, histone deacetylase inhibitors, and piperlongumine, which is known to have inhibitory effect on activity of NF-kB, were also identified. Some alkaloids were also selected as potential therapeutic drugs. These finding suggest that they might serve as a novel therapeutic option for anti-TNF refractory CD and support the use of public mol. data and computational approaches to discover novel therapeutic options for CD.

Scientific Reports 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

Lim, Soo-Jeong published the artcileAlpha-tocopheryl succinate sensitizes human colon cancer cells to exisulind-induced apoptosis, Name: Sulindac sulfone, the publication is Apoptosis (2007), 12(2), 423-431, database is CAplus and MEDLINE.

Sulindac sulfone (also known as exisulind) and its chem. derivatives are promising anticancer agents capable of inducing apoptosis in a variety of malignant cell types with minimal toxicity to normal cells. Here, we tested the ability of alpha-tocopheryl succinate (TOS), another promising anticancer agent, to sensitize colon cancer cells to exisulind-induced apoptosis. We found that sub-apoptotic doses of TOS greatly enhanced exisulind-induced growth suppression and apoptosis in the HCT116, LoVo and SNU-C4 human colon cancer cell lines. Our results revealed that this was accounted for primarily by an augmented cleavage of poly(ADP-ribose) polymerase (PARP) and enhanced activation of caspase-8, -9 and -3. Pretreatment with z-VAD-FMK (a pan-caspase inhibitor), z-IETD-FMK (a caspase-8 inhibitor) or z-LEHD-FMK (a caspase-9 inhibitor) blocked TOS and exisulind cotreatment-induced PARP cleavage and apoptosis. Furthermore, TOS/exisulind cotreatment induced JNK phosphorylation, while pretreatment with SP600151 (a JNK inhibitor) partially blocked cotreatment-induced caspase-dependent PARP cleavage and apoptosis. Taken together, these findings indicate that TOS sensitizes human colon cancer cells to exisulind-induced apoptosis. Apoptotic synergy induced by exisulind plus TOS seems likely to be mediated through a mechanism involving activation of caspases and JNK.

Apoptosis 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

Webster, W. Scott published the artcileExisulind in the treatment of prostate cancer, Recommanded Product: Sulindac sulfone, the publication is Expert Review of Anticancer Therapy (2005), 5(6), 957-962, database is CAplus and MEDLINE.

A review. Prostate cancer represents the most common noncutaneous malignancy in men. With the widespread use of prostate-specific antigen screening, as many as one in six men in the USA will be diagnosed with prostate cancer. Significant healthcare resources are currently devoted to the treatment of this disease, specifically aimed at improving the side effects of successful treatment. Surgery or radiation therapy provides the best chance of cure from this disease. However, as many as 50% of patients treated with curative intent will develop a recurrence 10-15 years following treatment. Hormonal ablation via medical or surgical castration provides disease control, but is associated with significant hot flushes, loss of libido and impotence. Selective, apoptotic antineoplastic drugs, such as exisulind, may provide an alternative method to treating or preventing prostate cancer. This drug profile reviews the evidence for the use of exisulind in the treatment of prostate cancer.

Expert Review of Anticancer 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 C5H5NO3S, Recommanded Product: Sulindac sulfone.

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

Romeiro, Nelilma C. published the artcileSynthesis, pharmacological evaluation and docking studies of new sulindac analogues, Product Details of C20H17FO4S, the publication is European Journal of Medicinal Chemistry (2009), 44(5), 1959-1971, database is CAplus and MEDLINE.

This paper describes the synthesis, pharmacol. evaluation and docking studies of a series of new sulindac analogs. Overall, the designed compounds revealed good, in vivo, antinociceptive activity and satisfactory anti-inflammatory profile. Flexible mol. docking with COX-1/COX-2 has shown putative binding modes of the designed compounds while the theor. evaluation of cell permeability based on Lipinski’s rule of five has helped rationalize the biol. results.

European Journal of Medicinal Chemistry 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, Product Details of C20H17FO4S.

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

Moon, Eun-Yi published the artcileBenzylamide sulindac analogues induce changes in cell shape, loss of microtubules and G₂-M arrest in a chronic lymphocytic leukemia (CLL) cell line and apoptosis in primary CLL cells, Computed Properties of 59973-80-7, the publication is Cancer Research (2002), 62(20), 5711-5719, database is CAplus and MEDLINE.

Given our interest in cyclic nucleotide phosphodiesterase inhibitors in chronic lymphocytic leukemia (CLL), we studied the effects of sulindac sulfone (exisulind), a non-cyclooxygenase-inhibitory end metabolite of the NSAID sulindac that has been reported to inhibit cGMP phosphodiesterases. We focused on a novel benzylamide analog of sulindac sulfone, CP461, which is in clin. trials as a chemotherapeutic agent. As previously reported for colon carcinoma cell lines, we found that CP461 induced a rise in cGMP levels and blocked cell proliferation in the CLL cell line WSU-CLL. Surprisingly, however, cell cycle anal. revealed that CP461 caused G₂-M arrest with an EC₅₀ of 1.1 渭M. G₂-M arrest was associated with phosphorylation of Bcl2 (but not BAD, Bax, or Bcl-XL): both of these end points were abrogated by treatment with a calcium chelator. Although CP461 induces p53 up-regulation, G₂-M arrest and Bcl2 phosphorylation were independent of p53. Because microtubule-active drugs such as vincristine also induced G₂-M arrest and Bcl2 phosphorylation in WSU-CLL, whereas the genotoxic drugs etoposide and doxorubicin did not, we examined the effect of CP461 on microtubules by indirect immunofluorescence microscopy. CP461 eliminated microtubules rapidly, with reduction detected within 30 min of drug treatment. CP461 also induced marked changes in cell shape. Neither sulindac sulfide (a cyclooxygenase inhibitor) nor sulindac sulfone induced G₂-M arrest, Bcl2 phosphorylation, microtubule disassembly, or cell shape changes. Treatment with 30 渭M CP461 induced greater than 50% apoptosis in 10 of 10 primary CLL leukemic cell samples, whereas the same drug concentration had only marginal effects (14% apoptosis) on whole mononuclear cells. Our work demonstrates that addition of a benzylamide moiety to sulindac compounds results in markedly altered pharmacol. properties that may be of use in the therapy of lymphoid malignancies.

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, Computed Properties of 59973-80-7.

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

Frahm, Silke published the artcileSulindac derivatives inhibit cell growth and induce apoptosis in primary cells from malignant peripheral nerve sheath tumors of NF1-patients, HPLC of Formula: 59973-80-7, the publication is Cancer Cell International (2004), No pp. given, database is CAplus.

Background: Malignant peripheral nerve sheath tumors (MPNSTs) are neoplasms leading to death in most cases. Patients with Neurofibromatosis type 1 have an increased risk of developing this malignancy. The metabolites of the inactive prodrug Sulindac, Sulindac Sulfide and Sulindac Sulfone (Exisulind) are new chemopreventive agents that show promising results in the treatment of different cancer types. In this study we examined the antineoplastic effect of these compounds on primary cells derived from two MPNSTs of Neurofibromatosis type 1 patients. Results: Exisulind and Sulindac Sulfide showed a dramatic time- and dose-dependent growth inhibitory effect with IC50-values of 120 渭M, and 63 渭M, resp. The decrease in viability of the tested cells correlated with induction of apoptosis. Treatment with 500 渭M Exisulind and 125 渭M Sulindac Sulfide for a period of 2 days increased the rate of apoptosis 21-27-fold compared to untreated cells. Reduced expression of RAS-GTP and phosphorylated ERK1/2 was detected in treated MPNST cells. Moreover, elevated levels of phosphorylated SAPK/JNK were found after drug treatment, and low activation of cleaved caspase-3 was seen. Conclusions: Our results suggest that this class of compounds may be of therapeutic benefit for Neurofibromatosis type 1 patients with MPNST.

Cancer Cell International 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

Jones, Suzanne F. published the artcileA phase I/II study of exisulind in combination with docetaxel/carboplatin in patients with metastatic non-small-cell lung cancer, Synthetic Route of 59973-80-7, the publication is Clinical Lung Cancer (2005), 6(6), 361-366, database is CAplus and MEDLINE.

Exisulind is a sulfone derivative of sulindac that induces apoptosis and demonstrates synergy with docetaxel in lung cancer models. This study evaluated the safety, efficacy, and pharmacokinetic interactions of exisulind and docetaxel/carboplatin in patients with metastatic non-small-cell lung cancer (NSCLC). Fifty-seven patients received 218 cycles of docetaxel (75 mg/m²) and carboplatin (area under the curve, 5.0) in combination with exisulind (125-250 mg orally twice daily). Two complete responses and 9 partial responses were observed among the 47 patients assessable for response (overall response rate, 23%). The median duration of response was 5.9 mo and median survival was 9.4 mo. The 1- and 2-yr survival rates are 35% and 14%, resp. The hematol. toxicities were consistent with those previously reported with docetaxel/carboplatin. The most common nonhematol. toxicities were mild to moderate fatigue, anorexia, nausea, and vomiting. The addition of exisulind to the chemotherapy regimen did not interfere with the metabolism or elimination of docetaxel and vice versa, and docetaxel did not interfere with the pharmacokinetic parameters of exisulind. This trial did not allow direct comparison of patients receiving docetaxel/carboplatin with and without exisulind, but when compared with historical data of docetaxel/carboplatin alone, the addition of exisulind does not appear to enhance antitumor activity, duration of response, or survival. Although preclin. data demonstrate increased apoptosis and prolonged survival for the combination of exisulind and docetaxel, multiple clin. trials do not support further clin. development of this combination regimen in patients with advanced NSCLC.

Clinical Lung Cancer 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, Synthetic Route of 59973-80-7.

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

Fredenhagen, Andreas published the artcileEvaluation of the optimization space for atmospheric pressure photoionization (APPI) in comparison with APCI, COA of Formula: C20H17FO4S, the publication is Journal of Mass Spectrometry (2014), 49(8), 727-736, database is CAplus and MEDLINE.

The usefulness of atm. pressure photoionization (APPI) is difficult to evaluate for unknowns due to the fragmented literature. Specifically, the variation of dopants with a wide set of compounds or the use of APPI in the neg. mode have rarely been explored. Thirty compounds were selected that were not suitable for ESI with a wide variety of functional groups and investigated with atm. pressure chem. ionization (APCI) and APPI in the pos. and neg. ion modes. The influence of the mobile phase (eluents containing acetonitrile or methanol) and – for APPI – four different dopants (acetone, chlorobenzene, toluene, and toluene/anisole) were explored. Stepwise variation of the organic mobile phase allowed to elucidate the ionization mechanism. Atm. pressure photoionization was especially useful for compounds, where the M^鈥? and not the [M + H]⁺ was formed. The dopants chlorobenzene and anisole promoted the formation of mol. ions M^鈥? for about half of the compounds, and its formation was also pos. influenced by the use of mobile phases containing methanol. In the neg. ion mode, APPI offered no advantage toward APCI. Best results were generally achieved with the dopant chlorobenzene, establishing that this dopant is suitable for a wide set of compounds For one quarter of the compounds, significantly better results were achieved with mobile phases containing methanol for both APPI and APCI than those with acetonitrile, but only in the pos. mode. With either of the methods – APPI or APCI – about 10% of the compounds were not detected. Strategies to get results quickly with difficult unknowns will be discussed.

Journal of Mass Spectrometry 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

Kapetanovic, I. M. published the artcileEffects of oral dosing paradigms (gavage versus diet) on pharmacokinetics and pharmacodynamics, Category: naphthyridine, the publication is Chemico-Biological Interactions (2006), 164(1-2), 68-75, database is CAplus and MEDLINE.

In cancer chemopreventive studies, test agents are typically administered via diet, while the preclin. safety studies normally employ oral gavage dosing. Correspondence in pharmacokinetic and pharmacodynamic profiles between the two dosing approaches cannot be assumed a priori. Sulindac, a non-steroidal anti-inflammatory agent with potential chemopreventive activity, was used to assess effects of the two oral dosing paradigms on its pharmacokinetics and pharmacodynamics. Time-dependent concentrations of sulindac and its sulfone metabolite were determined in plasma and potential target organ, mammary gland. Prostaglandin E₂ was used as a pharmacodynamic biomarker and measured in mammary gland. An inverse linear relationship was detected between pharmacodynamic and pharmacokinetic markers, area under the curve for prostaglandin E₂ levels and sulindac sulfone concentrations, resp., in the mammary tissue. Marked differences in pharmacokinetics and pharmacodynamics were observed after administration of sulindac by the two oral dosing paradigms. In general, oral gavage resulted in higher peak and lower trough concentrations of sulindac in plasma and mammary tissue, higher area under concentration-time curve in plasma and mammary tissue, and greater effect on prostaglandin E₂ levels than the corresponding diet dosing. This study illustrates potential pitfalls and limitations in trying to generalize based on data obtained with different oral dosing schemes and their extrapolation to potential efficacy and health risks in humans.

Chemico-Biological Interactions 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, Category: naphthyridine.

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