Tag: M.W=350-400

Curiel-Lewandrowski, Clara published the artcileRandomized, double-blind, placebo-controlled trial of sulindac in individuals at risk for melanoma Evaluation of potential chemopreventive activity, Quality Control of 59973-80-7, the publication is Cancer (Hoboken, NJ, United States) (2012), 118(23), 5848-5856, database is CAplus and MEDLINE.

BACKGROUND: : Reduced melanoma risk has been reported with regular use of nonsteroidal anti-inflammatory drugs (NSAIDs). However, the ability of NSAIDs to reach melanocytes in vivo and modulate key biomarkers in preneoplastic lesions such as atypical nevi has not been evaluated. METHODS: : This randomized, double-blind, placebo-controlled trial of sulindac was conducted in individuals with atypical nevi (AN) to determine bioavailability of sulindac and metabolites in nevi and effect on apoptosis and vascular endothelial growth factor A (VEGFA) expression in AN. Fifty subjects with AN ≥4 mm in size and 1 benign nevus (BN) were randomized to sulindac (150 mg twice a day) or placebo for 8 wk. Two AN were randomized for baseline excision, and 2 AN and BN were excised after intervention. RESULTS: : Postintervention sulindac, sulindac sulfone, and sulindac sulfide concentrations were 0.31 ± 0.36, 1.56 ± 1.35, and 2.25 ± 2.24 μg/mL in plasma, and 0.51 ± 1.05, 1.38 ± 2.86, and 0.12 ± 0.12 μg/g in BN, resp. Sulindac intervention did not significantly change VEGFA expression but did increase expression of the apoptotic marker cleaved caspase-3 in AN (increase of 3 ± 33 in sulindac vs decrease of 25 ± 45 in the placebo arm, P = .0056), although significance was attenuated (P = .1103) after adjusting for baseline expression. CONCLUSIONS: : Eight weeks of sulindac intervention resulted in high concentrations of sulindac sulfone, a proapoptotic metabolite, in BN but did not effectively modulate VEGFA and cleaved caspase-3 expression. Study limitations included limited exposure time to sulindac and the need to optimize a panel of biomarkers for NSAID intervention studies.

Cancer (Hoboken, NJ, United States) 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, Quality Control of 59973-80-7.

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

Skopinski, Piotr published the artcileSuppression of angiogenic activity of sera from diabetic patients with non-proliferative retinopathy by compounds of herbal origin and sulindac sulfone, Quality Control of 59973-80-7, the publication is International Journal of Molecular Medicine (2004), 14(4), 707-711, database is CAplus and MEDLINE.

Angiogenesis, the process of new blood vessel formation, is the key event in the mechanism of several pathol. processes including diabetic retinopathy. The physiol. control of angiogenesis depends on the balance between stimulatory and inhibitory factors. Therefore, a number of anti-angiogenic approaches has been developed, many of them based on the inhibition of the functional activity of pro-angiogenic factors. The aim of the present study was to compare the anti-angiogenic effectiveness of sulindac sulfone and some herbal compounds in the serum-induced angiogenesis test performed in Balb/c mice. Pooled sera from 35 patients with diabetes type 2 and retinopathy were used as pro-angiogenic stimuli. The strongest inhibitory effect was observed for the sulindac sulfone and ursolic acid in the highest concentration of 200 μg/mL, as well as for the low-dosage concomitant treatment with 2 μg/mL of epigallocatechin gallate (EGCG, green tea flavanol), ursolic acid (plant-derived triterpenoid), sulindac sulfone and convalamaroside (steroidal saponin). Combination treatment was significantly more effective than monotherapy with medium (20 μg/mL) or lowest doses of tested compounds The present study is the first to demonstrate the potent anti-angiogenic effect of the combination therapy comprising of plant-derived extracts and sulindac sulfone, as tested in the in vivo angiogenesis exptl. model with sera of non-proliferative diabetic retinopathy patients used as the pro-angiogenic stimuli. We think that it might be the first step toward application of some of these compounds, in the future, in preventive antiangiogenic therapy of these patients, as well, as in the treatment of later, proliferative stage of this disease.

International Journal of Molecular Medicine 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 C15H14O3, Quality Control of 59973-80-7.

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

Cho, H. published the artcileInhibition of NAD⁺-dependent 15-hydroxyprostaglandin dehydrogenase (15-PGDH) by cyclooxygenase inhibitors and chemopreventive agents, Quality Control of 59973-80-7, the publication is Prostaglandins, Leukotrienes and Essential Fatty Acids (2002), 67(6), 461-465, database is CAplus and MEDLINE.

15-Hydroxyprostaglandin dehydrogenase (15-PGDH) catalyzes NAD⁺-dependent oxidation of 15(S)-hydroxyl group of prostaglandins and has been considered a key enzyme involved in biol. inactivation of prostaglandins. This enzyme is markedly induced by androgens in hormone-sensitive human prostate cancer cells and may be involved in tumorigenesis. Inhibition of this enzyme may be of value in anticancer therapy. Non-steroidal anti-inflammatory drugs (NSAIDs) which inhibit cyclooxygenases (COXs) have been shown to be chemopreventive in epidemiol. and animal-model studies. However, chemoprevention by these drugs may not be directly related to their inhibition of COXs. Other targets may be also involved in their chemopreventive activity. The authors have examined a variety of NSAIDs including COX-2 selective inhibitors, peroxisome proliferator-activated receptor (PPAR) γ agonists and phytophenolic compounds which have been shown to be chemopreventive for their effect on 15-PGDH. It was found that most of these compounds were potent inhibitors of 15-PGDH. Among these compounds, ciglitazone appeared to be the most powerful inhibitor (IC₅₀=2.7 μM). Inhibition by ciglitazone was non-competitive with respect to NAD⁺ and uncompetitive with respect to PGE₂.

Prostaglandins, Leukotrienes and Essential Fatty Acids 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, Quality Control of 59973-80-7.

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

Nobuoka, Atsushi published the artcileGlutathione-S-transferase P1-1 protects aberrant crypt foci from apoptosis induced by deoxycholic acid, Recommanded Product: Sulindac sulfone, the publication is Gastroenterology (2004), 127(2), 428-443, database is CAplus and MEDLINE.

Background & Aims: Aberrant crypt foci, precursors of colonic adenoma, are frequently pos. for glutathione-S-transferase P1-1. Because deoxycholic acid is an apoptosis-inducing xenobiotic in the colon, the authors examined the possibility that aberrant crypt foci, through the cytoprotecting function of glutathione-S-transferase P1-1, resist deoxycholic acid-induced apoptosis, thereby surviving to become adenomas and subsequently cancer. Methods: Glutathione-S-transferase P1-1 or cyclooxygenase-2 expression and the percentage of apoptotic cells in aberrant crypt foci were examined by immunohistochem. and by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling, resp. Glutathione-S-transferase P1-1 was transfected into colon cancer cells (M7609) and human lung fibroblasts, and deoxycholic acid-induced apoptosis was evaluated by a dye-uptake assay and flow cytometry. Binding of deoxycholic acid to glutathione-S-transferase P1-1 was analyzed by CD and immunoprecipitation Caspase activities were determined by colorimetric protease assay, and sulindac binding to glutathione-S-transferase P1-1 was determined by inhibition assay of glutathione-S-transferase P1-1 activity. Results: Aberrant crypt foci showed pos. immunostaining for glutathione-S-transferase P1-1 but neg. staining for cyclooxygenase-2. The percentage of apoptotic cells in aberrant crypt foci was significantly lower than in healthy epithelium, and the difference became more apparent with deoxycholic acid treatment. The impaired sensitivity of aberrant crypt foci to deoxycholic acid was restored by the glutathione-S-transferase P1-1-specific inhibitor γ-glutamyl-S-(benzyl)cysteinyl-R-phenylglycine diethylester. By transfection of glutathione-S-transferase P1-1, M7609 cells became more resistant to deoxycholic acid-induced apoptosis than mock transfectants. Direct binding of glutathione-S-transferase P1-1 to deoxycholic acid was proven by CD and by immunoprecipitation The aberrant crypt foci in adenoma patients treated with sulindac, which was shown to bind to glutathione-S-transferase P1-1, underwent apoptosis in 4 days and mostly regressed in 2-3 mo. Conclusions: Glutathione-S-transferase P1-1 protects aberrant crypt foci from deoxycholic acid-induced apoptosis and may play a pivotal role in early colon carcinogenesis.

Gastroenterology 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

Sheng, Huaming published the artcileIdentification of N-Oxide and Sulfoxide Functionalities in Protonated Drug Metabolites by Using Ion-Molecule Reactions Followed by Collisionally Activated Dissociation in a Linear Quadrupole Ion Trap Mass Spectrometer, SDS of cas: 59973-80-7, the publication is Journal of Organic Chemistry (2016), 81(2), 575-586, database is CAplus and MEDLINE.

The in vivo oxidation of sulfur and nitrogen atoms in many drugs into sulfoxide and N-oxide functionalities is a common biotransformation process. Unfortunately, the unambiguous identification of these metabolites can be challenging. In the present study, ion-mol. reactions of tris(dimethylamino)borane followed by collisionally activated dissociation (CAD) in an ion trap mass spectrometer are demonstrated to allow the identification of N-oxide and sulfoxide functionalities in protonated polyfunctional drug metabolites. Only ions with N-oxide or sulfoxide functionality formed diagnostic adducts that had lost di-Me amine (DMA). This was demonstrated even for an analyte that contains a substantially more basic functionality than the functional group of interest. CAD of the diagnostic product ions (M) resulted mainly in type A (M – DMA) and B fragment ions (M – HO-B(N(CH₃)₂)₂) for N-oxides, but sulfoxides also formed diagnostic C ions (M – O=BN(CH₃)₂), thus allowing differentiation of the functionalities. Some protonated analytes yielded abundant TDMAB adducts that had lost two DMA mols. instead of just one. This provides information on the environment of the N-oxide and sulfoxide functionalities. Quantum chem. calculations were performed to explore the mechanisms of the above-mentioned reactions. The method can be implemented on HPLC for real drug anal.

Journal of Organic 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 C17H18N3NaO3S, SDS of cas: 59973-80-7.

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

Li, Jing published the artcilemTORC1-Driven Tumor Cells Are Highly Sensitive to Therapeutic Targeting by Antagonists of Oxidative Stress, Name: Sulindac sulfone, the publication is Cancer Research (2016), 76(16), 4816-4827, database is CAplus and MEDLINE.

MTORC1 is a central signaling node in controlling cell growth, proliferation, and metabolism that is aberrantly activated in cancers and certain cancer-associated genetic disorders, such as tuberous sclerosis complex (TSC) and sporadic lymphangioleiomyomatosis. However, while mTORC1-inhibitory compounds (rapamycin and rapalogs) attracted interest as candidate therapeutics, clin. trials have not replicated the promising findings in preclin. models, perhaps because these compounds tend to limit cell proliferation without inducing cell death. In seeking to address this issue, we performed a high-throughput screen for small mols. that could heighten the cytotoxicity of mTORC1 inhibitors. Here we report the discovery that combining inhibitors of mTORC1 and glutamate cysteine ligase (GCLC) can selectively and efficiently trigger apoptosis in Tsc2-deficient cells but not wild-type cells. Mechanistic investigations revealed that coinhibition of mTORC1 and GCLC decreased the level of the intracellular thiol antioxidant glutathione (GSH), thereby increasing levels of reactive oxygen species, which we determined to mediate cell death in Tsc2-deficient cells. Our findings offer preclin. proof of concept for a strategy to selectively increase the cytotoxicity of mTORC1 inhibitors as a therapy to eradicate tumor cells marked by high mTORC1 signaling, based on cotargeting a GSH-controlled oxidative stress pathway. Cancer Res; 76(16); 4816-27. ©2016 AACR.

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

Elmore, Eugene published the artcileCorrelation of in vitro chemopreventive efficacy data from the human epidermal cell assay with animal efficacy data and clinical trial plasma levels, Category: naphthyridine, the publication is Journal of Cellular Biochemistry (2005), 95(3), 571-588, database is CAplus and MEDLINE.

The human epidermal cell (HEC) assay, which uses carcinogen exposed normal skin keratinocytes to screen for cancer prevention efficacy, was used to screen possible preventive agents. The endpoints measured were inhibition of carcinogen-induced growth and induction of involucrin, an early marker of differentiation. Sixteen of twenty agents (apigenin, apomine, budesonide, N-(2-carboxyphenyl)retinamide, ellagic acid, ibuprofen, indomethacin, melatonin, (-)-2-oxo-4-thiazolidine carboxylic acid, polyphenon E, resveratrol, β-sitosterol, sulfasalazine, vitamin E acetate, and zileuton) were pos. in at least one of the two assay endpoints. Four agents (4-methoxyphenol, naringenin, palmitoylcarnitine chloride, and silymarin) were neg. in the assay. Nine of the sixteen agents were pos. for both endpoints. Agents that showed the greatest response included: ellagic acid > budesonide, ibuprofen > apigenin, and quinicrine dihydrochloride. Fifty-eight of sixty-five agents that have been evaluated in the HEC assay have also been evaluated in one or more rodent bioassays for cancer prevention and several are in clin. trials for cancer prevention. The assay has an overall predictive accuracy of ∼91.4% for efficacy in rodent cancer prevention irresp. of the species used, the tissue model, or the carcinogen used. Comparison of the efficacious concentrations in vitro to plasma levels in clin. trials show that concentrations that produced efficacy in the HEC assay were achieved in clin. studies for 31 of 33 agents for which plasma levels and/or C_max levels were available. For two agents, 9-cis-retinoic acid (RA) and dehydroepiandrosterone (DHEA), the plasma levels greatly exceeded the highest concentration (HC) found to have efficacy in vitro. Thus, the HEC assay has an excellent predictive potential for animal efficacy and is responsive at clin. achievable concentrations

Journal of Cellular Biochemistry 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

Deguchi, Atsuko published the artcileVasodilator-stimulated phosphoprotein (VASP) phosphorylation provides a biomarker for the action of exisulind and related agents that activate protein kinase G, Application In Synthesis of 59973-80-7, the publication is Molecular Cancer Therapeutics (2002), 1(10), 803-809, database is CAplus and MEDLINE.

Recent studies provide evidence that exisulind and two potent derivatives, CP461 and CP248, induce apoptosis in colon cancer cells by inhibiting cGMP-specific phosphodiesterases (phosphodiesterases 2 and 5). This causes an increase in intracellular levels of cGMP, thus activating the cGMP-dependent protein kinase G (PKG), which then activates pathways that lead to apoptosis. To further examine this mechanism and to provide a potential in vivo biomarker for activation of this pathway, we examined phosphorylation of the vasodilator-stimulated phosphoprotein (VASP), a ubiquitously expressed endogenous substrate for PKG. We found that VASP was phosphorylated after treating SW480 colon cancer cells with exisulind, CP461, or CP248. CP248-induced VASP phosphorylation was inhibited by a specific PKG inhibitor but not by a protein kinase A inhibitor. The drug 3-(5′-hydroxymethyl-2′-furyl)benzylindazole and nitric oxide donors that activate cellular guanylyl cyclase and thus increase cellular levels of cGMP also caused VASP phosphorylation. With all of these agents, the phosphorylation of VASP was associated with increased intracellular levels of cGMP and the induction of apoptosis. We also demonstrated direct in vivo phosphorylation of VASP with constitutively activated mutants of PKG. These results suggest that VASP phosphorylation can provide a useful endogenous cellular biomarker for anticancer agents that cause cGMP-mediated apoptosis.

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, Application In Synthesis of 59973-80-7.

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

Elwich-Flis, S. published the artcileAnti-Angiogenic and Apoptotic Effects of Metabolites of Sulindac on Chick Embryo Chorioallantoic Membrane, Related Products of naphthyridine, the publication is Hybridoma and Hybridomics (2003), 22(1), 55-60, database is CAplus and MEDLINE.

Sulindac and other nonsteroidal anti-inflammatory drugs (NSAIDs), in addition to anti-inflammatory properties, express preventive activity against colon cancer. This antineoplastic effect may result from the suppression of polyp development in patients with familial adenomatous polyposis. However, despite intense investigations the exact mechanism for sulindac protective effect is not fully elucidated. Angiogenesis, the process of new blood vessel formation, is required to support tumor growth and may be partially involved in the transformation of polyps into tumor. Therefore, we tested the hypothesis whether sulindac might inhibit angiogenesis. The effects of sulindac metabolites, sulindac sulfide and sulindac sulfone, on vascular development were evaluated using the chick embryo chorioallantoic membrane (CAM) assay in vivo. The angiogenic response was quantitated by several methods including direct stereomicroscopic observation, measurements of Hb content and DNA synthesis whereas quantitation of apoptosis was based on determinations of caspase-3 activity, caspase-3 and bax protein expression, and nuclear DNA fragmentation. Our results indicated that both sulindac metabolites were equally effective in inhibition of new blood vessel formation in CAM during chick embryo development. Moreover, both metabolites of sulindac induced apoptosis in parallel with inhibition of angiogenesis.

Hybridoma and Hybridomics 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, Related Products of naphthyridine.

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

Sauter, Alexander published the artcileSulindac sulfone induces a decrease of β-catenin in HNSCC, Synthetic Route of 59973-80-7, the publication is Anticancer Research (2010), 30(2), 339-344, database is CAplus.

Background: The most common neoplasm arising in the upper gastrointestinal tract is head and neck squamous cell carcinoma (HNSCC). This is an aggressive epithelial malignancy. Many growth factors and cytokines have been discovered that are responsible for the growth and formation of tumors. Among these factors, β-catenin is considered to be the most important for reducing cell-cell adhesions in malignant tissue. The degradation of β-catenin triggers apoptosis by different routes. Sulindac sulfone has been shown to induce apoptosis in several different tumors. In the present study, we surveyed the concentration of β-catenin in an HNSCC line after incubation with different concentrations of sulindac sulfone. Materials and Methods: Immunohistochem. and Western blot analyses were performed after treatment of the UMSCC 11A cell line with different concentrations of sulindac sulfone (100, 200, 400, 600 and 800 μMol) for 48 h. Results: At 100 μMol of sulindac sulfone, a decrease in β-catenin concentration of 5% was observed; increasing concentrations of sulindac sulfone resulted in >70% reduction in secreted β-catenin. Thus in conclusion, incubation with sulindac sulfone seemed to stop proliferation. With respect to the controls, there was no greater reduction in total protein. Conclusion: In this study, sulindac sulfone reduced levels of secreted β-catenin in the HNSCC cell line UM-SCC 11A after 48 h of incubation. It is presumed that reduction of cell-cell adhesion, which is predominately affected by β-catenin, is an essential step in the progression from localized malignancy to stromal and vascular invasion and ultimately metastatic disease. The reduction in the level of mural expression of β-catenin has been associated with loss of differentiation in laryngeal carcinomas. Thus, prevention of intracellular β-catenin accumulation is regarded as an attractive target for chemopreventive agents.

Anticancer 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, Synthetic Route of 59973-80-7.

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