Tag: M.W=350-400

Ryan, Christopher W. published the artcileA phase I/II dose-escalation study of exisulind and docetaxel in patients with hormone-refractory prostate cancer, Application of Sulindac sulfone, the publication is BJU International (2005), 95(7), 963-968, database is CAplus and MEDLINE.

OBJECTIVE: To determine the safety and efficacy, in a dose-escalation study, of exisulind (an oral sulfone metabolite of sulindac thought to induce apoptosis in malignant cells by inhibiting cGMP-phosphodiesterase) combined with docetaxel in men with hormone-refractory prostate cancer (HRPC), as pre-clin. studies suggested activity against prostate cancer and synergy with cytotoxic agents. PATIENTS AND METHODS: Thirty-four patients with HRPC were treated with oral exisulind twice daily for 21-day cycles and i.v. docetaxel given for 1 h on the first day of each cycle. Three dose levels were assessed, combining exisulind 150 and 250 mg twice daily with docetaxel at 60 or 75 mg/m². Toxicity was then evaluated using standard criteria. RESULTS: The recommended phase II dose was determined to be exisulind 250 mg and docetaxel 60 mg/m², with escalation to 75 mg/m² after cycle 1, as tolerated. The most common grade 3-4 toxicities among all patients were neutropenia (56%), infection (24%) and hyperglycemia (18%). Twelve of 32 evaluable patients (38%, 95% confidence interval, CI, 23-55%) had a decline in PSA by at least half. Only four of 17 evaluable patients (95% CI, 1-47%) treated at the phase II dose level had such a decline in PSA. The median (95% CI) overall survival of all patients was 16 (12.9-19.7) months and median progression-free survival 4.7 (2.7-5.2) months. CONCLUSION: The combination of exisulind and docetaxel was tolerable in patients with HRPC. The PSA response rates do not suggest an improvement over historical data with single-agent docetaxel in this population.

BJU 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, Application of Sulindac sulfone.

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

Agarwal, B. published the artcileCox-2 is needed but not sufficient for apoptosis induced by Cox-2 selective inhibitors in colon cancer cells, COA of Formula: C20H17FO4S, the publication is Apoptosis (2003), 8(6), 649-654, database is CAplus and MEDLINE.

The role of Cox-2 in NSAID-induced apoptosis is debated. We studied the role of Cox-2 inhibition in apoptosis induced by a selective Cox-2 inhibitor, SC 236 (a structural analog of celecoxib) in two colon cancer cell lines, HT29 (expressing Cox-2 protein) and HCT116 (not expressing Cox-2 protein). Apoptosis was quantified by flow cytometry. SC 236 0-75 μM decreased cell numbers and induced apoptosis to identical levels in HT29 and HCT116 cells. However, SC 236, concentrations >75 μM reduced Cox-2 protein expression in HT29 cells and induced greater levels of apoptosis in HT29 than in HCT116 cells. In contrast, sulindac sulfide (SSD) (which inhibits Cox-1 and Cox-2) 0-200 μM or sulindac sulfone (SSN) 0-500 μM (without significant activity against Cox-1 or Cox-2) caused identical decreases in cell number and increases in apoptosis in HT29 and HCT116 cells. Neither SSD nor SSN altered the expression of Cox-2 in HT29 cells. To determine that the higher levels of apoptosis in HT29 cells with SC 236 >75 μM were related to decreased Cox-2 protein levels, we decreased Cox-2 protein expression in HT29 cells with curcumin (diferuloylmethane) and studied its effect on SC 236-induced apoptosis. Curcumin augmented apoptosis induced by SC 236 in HT29 cells but not in Cox-2 lacking HCT116 cells. In conclusion, selective Cox-2 inhibitors can induce apoptosis independent of Cox-2 expression. However they may selectively target cells that express Cox-2 by decreasing their Cox-2 protein expression.

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, COA of Formula: C20H17FO4S.

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

Quidville, Virginie published the artcile15-Hydroxyprostaglandin-dehydrogenase is involved in anti-proliferative effect of non-steroidal anti-inflammatory drugs COX-1 inhibitors on a human medullary thyroid carcinoma cell line, Recommanded Product: Sulindac sulfone, the publication is Prostaglandins & Other Lipid Mediators (2006), 81(1-2), 14-30, database is CAplus and MEDLINE.

Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit prostaglandin (PG) synthesis enzymes, the cyclooxygenases (COX-1 and 2). It is suggested that these enzymes are not their only targets. We reported that in tumoral TT cell, indomethacin, in vivo and in vitro, decreases proliferation and increases activity of 15-hydroxyprostaglandin-dehydrogenase (15-PGDH), the PG catabolism key enzyme. Here, we show that the COX-1 inhibitors, selective or not, and sulindac sulfone, a non-COX inhibitor, increased 15-PGDH activity and reduced PGE₂ levels. This increase was neg. correlated to the decrease in cell proliferation and suggested that 15-PGDH could be implicated in NSAIDs anti-proliferative effect. Indeed, the silencing of 15-PGDH expression by RNA interference using 15-PGDH specific siRNA enhanced TT cell proliferation and abolished the anti-proliferative effect of a representative non-selective inhibitor, ibuprofen. Moreover, a specific inhibitor of 15-PGDH activity, CAY 10397, completely reversed the effect of ibuprofen on proliferation. Consequently our results demonstrate that, at least in TT cells, 15-PGDH is implicated in proliferation and could be a target for COX-1 inhibitors specific or not. NSAIDs defined by their COX inhibition should also be defined by their effect on 15-PGDH.

Prostaglandins & Other Lipid Mediators 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

Huang, Wei-Hua published the artcileSimultaneous determination of sulindac and its metabolites sulindac sulfide and sulindac sulfone in human plasma by a sensitive UPLC-PDA method for a pharmacokinetic study, Synthetic Route of 59973-80-7, the publication is Analytical Methods (2014), 6(13), 4679-4685, database is CAplus.

A sensitive, rapid and reliable ultra-performance liquid chromatog. (UPLC) with Photo-Diode Array (PDA) detection method was developed for simultaneous determination of sulindac and its metabolites sulindac sulfide and sulindac sulfone in human plasma. The analytes were extracted by dichloromethane from human plasma using a liquid-liquid extraction method. The chromatog. separation was performed on a Waters Acquity UPLC with a Waters Acquity UPLC BEH C₁₈ column (2.1 × 50 mm i.d., 1.7 μm) within 5 min. The mobile phase used for gradient elution consisted of ammonium formate buffer (20 mM) containing 1% acetic acid and acetonitrile. The flow rate was maintained at 0.4 mL min^-1. The monitor wavelength was set at 328 nm for PDA detection. All calibration curves of the analytes showed good linearity within the test ranges. The validated method was successfully applied to a pharmacokinetic study of sulindac, sulindac sulfide and sulindac sulfone in 15 healthy Chinese male subjects with oral administration of sulindac tablets.

Analytical Methods 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

Tang, Weijuan published the artcileGas-phase ion-molecule reactions for the identification of the sulfone functionality in protonated analytes in a linear quadrupole ion trap mass spectrometer, Application In Synthesis of 59973-80-7, the publication is Rapid Communications in Mass Spectrometry (2016), 30(12), 1435-1441, database is CAplus and MEDLINE.

Rationale : The oxidation of sulfur atoms is an important biotransformation pathway for many sulfur-containing drugs. In order to rapidly identify the sulfone functionality in drug metabolites, a tandem mass spectrometric method based on ion-mol. reactions was developed. Methods : A phosphorus-containing reagent, tri-Me phosphite (TMP), was allowed to react with protonated analytes with various functionalities in a linear quadrupole ion trap mass spectrometer. The reaction products and reaction efficiencies were measured. Results : Only protonated sulfone model compounds were found to react with TMP to form a characteristic [TMP adduct-MeOH] product ion. All other protonated compounds investigated, with functionalities such as sulfoxide, N-oxide, hydroxylamino, keto, carboxylic acid, and aliphatic and aromatic amino, only react with TMP via proton transfer and/or addition The specificity of the reaction was further demonstrated by using a sulfoxide-containing anti-inflammatory drug, sulindac, as well as its metabolite sulindac sulfone. Conclusions : A method based on functional group-selective ion-mol. reactions in a linear quadrupole ion trap mass spectrometer has been demonstrated for the identification of the sulfone functionality in protonated analytes. A characteristic [TMP adduct-MeOH] product ion was only formed for the protonated sulfone analytes. The applicability of the TMP reagent in identifying sulfone functionalities in drug metabolites was also demonstrated. Copyright © 2016 John Wiley & Sons, Ltd.

Rapid Communications in 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 C26H45N5O7Si2, Application In Synthesis of 59973-80-7.

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

Galmarini, Carlos M. published the artcileOSI-461 (OSI), COA of Formula: C20H17FO4S, the publication is Current Opinion in Investigational Drugs (Thomson Scientific) (2004), 5(6), 648-656, database is CAplus and MEDLINE.

A review. OSI Pharmaceuticals is developing OSI-461, a potent analog of exisulind, for the potential treatment of cancer and inflammatory bowel disease. In August 2001, OSI-461 entered phase II trials involving patients with chronic lymphocytic leukemia. In July 2002, the company embarked on a pilot phase II study evaluating OSI-461 for the treatment of Crohn’s disease. By Oct. 2002, Cell Pathways had selected hormone-refractory prostate cancer as the lead cancer indication for clin. development of OSI-461.

Current Opinion in Investigational Drugs (Thomson Scientific) 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

Levine, Lawrence published the artcileDoes the release of arachidonic acid from cells play a role in cancer chemoprevention?, Recommanded Product: Sulindac sulfone, the publication is FASEB Journal (2003), 17(8), 800-802, database is CAplus and MEDLINE.

COX-2 is overexpressed in cancer cells and has become a major target for cancer preventive drugs. NSAIDs, retinoids, antioxidants, and PPAR agonists, reported to be chemopreventive, suppress COX-2 synthesis. NSAIDs also have been shown to be chemopreventive independent of COX-2 activity. Common to all of these compounds is their ability to release arachidonic acid (AA) from rat liver cells in culture. Most of these compounds inhibit induced PGI₂ production Vitamin D₃ and tamoxifen, however, not only stimulate the release of AA from cells: they amplify rather than inhibits induced COX activity. In view of the many activities attributable to AA, I propose that its release and accumulation could initiate mol. reactions that lead to apoptosis and eventually to suppression of cancer. Some drugs shown to release AA from cells and affect PGI₂ production-e.g., thiazolidinediones and statins are widely used for conditions unrelated to cancer. In vivo studies could reveal whether they can also function as cancer preventive agents.

FASEB Journal 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

Malkinson, Alvin M. published the artcileRole of inflammation in mouse lung tumorigenesis: a review, Application of Sulindac sulfone, the publication is Experimental Lung Research (2005), 31(1), 57-82, database is CAplus and MEDLINE.

A review. Peritumoral and intratumoral macrophages are associated with human and mouse lung cancer. The mouse model allows manipulation of the macrophage population to exptl. evaluate its contribution to tumor growth. Genetic and pharmacol. strategies also permit testing the involvement of specific inflammatory mediators in tumor progression. Among those endogenous mediators thus identified are interleukin (IL)-10, glucocorticoids, prostacyclin, nitric oxide, and surfactant apoprotein D (SP-D); serum SP-D levels are a useful biomarker to monitor tumor growth rate. The importance of understanding the mutually antagonistic roles of individual prostaglandins downstream from cycloxygenase (COX) and how this affects the efficacy of COX-inhibitory drugs is discussed. Promising drug candidates include synthetic glucocorticoids such as budesonide and the sulfone derivative of sulindac, apotosyn.

Experimental Lung 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, Application of Sulindac sulfone.

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

Masuda, Yasusuke published the artcileIntrahepatic flow disturbance: possibility of a hidden cause of drug toxicity, Synthetic Route of 59973-80-7, the publication is Journal of Pharmacological Sciences (Tokyo, Japan) (2006), 100(3), 167-174, database is CAplus and MEDLINE.

The liver has an intricate microvascular system that allows homogenous perfusion throughout the organ. However, the regulatory mechanisms of intrahepatic circulation are still unclear, and the effects of drugs on this system have rarely been reported. Oxethazaine, a topical anesthetic, was incidentally found to induce a consistent increase in portal pressure in the isolated perfused rat liver, which led us to characterize this phenomenon. For this, a vital staining method was developed to detect microcirculatory alterations in the isolated liver. Using this method, not only vasoconstrictors like endothelin-1, but the drugs oxethazaine and clomipramine, a tricyclic antidepressant, were found to induce flow redistribution to the deeper and hilar portions of the liver with minimal perfusion at the periphery, which was due to a short-circuit flow at the center owing to the constriction of the intrahepatic portal vein branches. Hepatic nerve stimulation also produced a similar flow disturbance. Since the portal pressure increases by these compounds were inhibited by the Rho-kinase inhibitors Y27632 and HA1077, portal vein branches may employ a Rho-kinase-dependent pathway for sustained contraction. However, oxethazaine, clomipramine, and endothelin-1 may activate this pathway differently. The intrahepatic flow disturbance could play a hidden role in drug toxicity of certain drugs.

Journal of Pharmacological Sciences (Tokyo, Japan) 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

Andrews, Peter published the artcileA comparison of the effectiveness of selected non-steroidal anti-inflammatory drugs and their derivatives against cancer cells in vitro, Recommanded Product: Sulindac sulfone, the publication is Cancer Chemotherapy and Pharmacology (2008), 61(2), 203-214, database is CAplus and MEDLINE.

Previously, we reported in vitro observations suggesting that ibuprofen is an effective non-prescription non-steroidal anti-inflammatory drug (NSAID) to reduce the survival of human prostate cancer cells (Andrews et al. in Cancer Chemother Pharmacol 502:77-284, 2002), and that this observed effectiveness is mediated by an up-regulation of the p75^NTR tumor suppressor (Khwaja et al. in Cancer Res 646:207-6213, 2004). However, other NSAIDs and their derivatives have received significant attention with regard to their anti-cancer effectiveness and have been selected for clin. trials to treat a variety of human cancers. In this investigation, we compared celecoxib, sulindac sulfone, nitric oxide linked NSAIDs, and R-flurbiprofen with ibuprofen in their ability to inhibit the growth of a variety of human cancer cells lines including cells lines with multi-drug resistance. We also evaluated whether, like ibuprofen, an up-regulation of p75^NTR is a mol. mechanism that mediates the anti-growth effectiveness of these drugs. Selected dosages for each drug were evaluated for their ability to reduce the growth (MTT anal.) and induce apoptosis (Hoechst staining) of a variety of different cancer cell lines, including an ovarian cell line expressing multidrug resistance-1 glycoprotein (MDR-1). The drugs were then analyzed using immunoblot, RT-PCR and siRNA to study the role of p75^NTR in their anti-growth effectiveness. This study revealed consistency in the drug dosages that inhibit the survival of different human cancer cell lines. While NO-linked aspirin and celecoxib were most effective in decreasing cell growth and inducing apoptosis at the lowest dosages, R-flurbiprofen and ibuprofen were most effective at clin. relevant dosages. A multidrug resistant ovarian cell line is more resistant to growth inhibition by the drugs tested than its non-drug resistant parental counterpart. There was no correlation between the expression of cyclooxygenase-2 (COX-2) and the ability of the drugs to reduce cancer cell survival. All the drugs tested induced an up-regulation in p75^NTR tumor suppressor gene expression in concert with their observed growth inhibiting ability. Inhibition of p75^NTR expression with siRNA reduced the cell growth inhibiting effects of all the drugs tested. The method of chemotherapy (i.e., intravascular, intrathecal, oral) might dictate the choice of NSAID/NSAID derivative used to treat/prevent a given type of cancer. Also, the p75^NTR tumor suppressor appears to be a common mol. mechanism that mediates the growth inhibiting effectiveness of these drugs.

Cancer Chemotherapy and Pharmacology 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