Tag: M.W=350-400

Zerbini, Luiz F. published the artcileA Novel Pathway Involving Melanoma Differentiation Associated Gene-7/Interleukin-24 Mediates Nonsteroidal Anti-inflammatory Drug-Induced Apoptosis and Growth Arrest of Cancer Cells, HPLC of Formula: 59973-80-7, the publication is Cancer Research (2006), 66(24), 11922-11931, database is CAplus and MEDLINE.

Numerous studies show that nonsteroidal anti-inflammatory drugs (NSAIDs) are effective in chemoprevention or treatment of cancer. Nevertheless, the mechanisms underlying these antineoplastic effects remain poorly understood. Here, we report that induction of the cancer-specific proapoptotic cytokine melanoma differentiation associated gene-7/interleukin-24 (MDA-7/IL-24) by several NSAIDs is an essential step for induction of apoptosis and G₂-M growth arrest in cancer cells in vitro and inhibition of tumor growth in vivo. We also show that MDA-7/IL-24-dependent up-regulation of growth arrest and DNA damage inducible 45 α (GADD45α) and GADD45γ gene expression is sufficient for cancer cell apoptosis via c-Jun NH₂-terminal kinase (JNK) activation and growth arrest induction through inhibition of Cdc2-cyclin B checkpoint kinase. Knockdown of GADD45α and GADD45γ transcription by small interfering RNA abrogates apoptosis and growth arrest induction by the NSAID treatment, blocks JNK activation, and restores Cdc2-cyclin B kinase activity. Our results establish MDA-7/IL-24 and GADD45α and GADD45γ as critical mediators of apoptosis and growth arrest in response to NSAIDs in cancer cells.

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 C7H5BFNO2, HPLC of Formula: 59973-80-7.

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

Cen, Bo published the artcileActivation of Protein Kinase G Increases the Expression of p21^CIP1, p27^KIP1, and Histidine Triad Protein 1 through Sp1, Quality Control of 59973-80-7, the publication is Cancer Research (2008), 68(13), 5355-5362, database is CAplus and MEDLINE.

The anticancer role of cyclic guanosine 3′,5′-monophosphate (cGMP)-dependent protein kinase G (PKG) has become of considerable interest, but the underlying mechanisms are not fully established. In this study, we examined the effects of activation of PKG on the expression of three tumor suppressor proteins in human SW480 colon cancer cells. Our results revealed that treatment with cell permeable cGMP derivatives, or the cGMP phosphodiesterase inhibitor sulindac sulfone (exisulind, aptosyn, hereafter called exisulind) led to increased expression of the tumor suppressor proteins p21^CIP1, p27^KIP1, and Histidine triad protein 1 (HINT1), and their corresponding mRNAs. Overexpression of PKG Iβ also caused increased expression of the p21^CIP1, p27^KIP1, and HINT1 proteins. Both the p21^CIP1 and p27^KIP1 promoters contain Sp1 binding sites and they were activated by PKG in luciferase reporter assays. Specific Sp1 sites in the p21 and p27 promoters were sufficient to mediate PKG-induced luciferase reporter activity, suggesting an interaction between Sp1 and PKG. Indeed, we found that PKG can phosphorylate Sp1 on serine residue(s) and this resulted in transcriptional activation of Sp1. Knockdown of Sp1 expression with siRNA inhibited the increased expression of p21^CIP1, p27^KIP1, and HINT1 induced by the cGMP derivative 8-pCPT-cGMP in SW480 cells. These novel effects of PKG activation on the expression of three tumor suppressor genes may explain, at least in part, the anticancer effects of activation of PKG. They also provide a rationale for further developing activators of PKG for the prevention and treatment of cancer.

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, Quality Control of 59973-80-7.

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

Xiao, Danhua published the artcileThe sulindac derivatives OSI-461, OSIP486823, and OSIP487703 arrest colon cancer cells in mitosis by causing microtubule depolymerization, Product Details of C20H17FO4S, the publication is Molecular Cancer Therapeutics (2006), 5(1), 60-67, database is CAplus and MEDLINE.

Exisulind (sulindac sulfone) and three highly potent derivatives, OSI-461 (CP461), OSIP486823 (CP248), and OSIP487703, inhibit growth and induce apoptosis in SW480 human colon cancer cells, with IC₅₀s of 200, 2, 0.1, and 0.003 μmol/L, resp. The latter three compounds, but not exisulind, induce marked M-phase cell cycle arrest in these cells. This effect seems to be independent of the known ability of these compounds to cause activation of protein kinase G. When tested at twice their IC₅₀ concentration for growth inhibition, OSI-461, OSIP486823, and OSIP487703 cause depolymerization of microtubules in interphase cells, inhibit spindle formation in mitotic cells, and induce multinucleated cells. In vitro tubulin polymerization assays indicate that all three compounds interact with tubulin directly to cause microtubule depolymerization and/or inhibit de novo tubulin polymerization These results suggest that the dual effects of OSI-461, OSIP486823, and OSIP487703 on impairment of microtubule functions and protein kinase G activation may explain the potent antiproliferative and apoptotic effects of these compounds in cancer cells.

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 C12H15NO, Product Details of C20H17FO4S.

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

Naim, Ramin published the artcileChemopreventive alteration of the cell-cell adhesion in head and neck squamous cell cancer, Recommanded Product: Sulindac sulfone, the publication is Oncology Reports (2006), 16(2), 273-277, database is CAplus and MEDLINE.

Approx. 310,000 new cases of oral and pharynx cancer account for a major cause of neoplasm related morbidity and mortality world-wide. Unfortunately, the survival rate has not improved significantly in the last decade. The vast majority of head and neck cancer is squamous cell carcinoma. The major adhesion-proteins involved in the development and maintenance of all solid tissue are the Cadherins. Cadherins are the transmembrane components of the adherent junction with interaction with plakoglobin and β-catenin. Downregulation of Cadherins and catenins is frequently observed in many types of human cancer. Sulindac sulfone is one of the new therapeutic apoptotic agents that show promise in the treatment of cancer. In this study, the authors incubated sulindac sulfone with a head and neck cancer cell line and investigated the outcome of E-Cadherin. Immunohistochem. and Western blot analyses were then performed, with different concentrations of sulindac sulfone (100, 200, 400, 600, and 800 μMol) for 48 h. At 400 μMol of sulindac sulfone a decrease of 21% was observed; at 600 μMol, 44% decrease of β-catenin concentration was seen, and incubation with 800 μMol resulted in 73% reduction of secreted β-catenin. Incubation with sulindac sulfone seemed to stop proliferation; however, with respect to the controls, there was no increased reduction of the total protein. Sulindac sulfone resulted in an increase of E-Cadherin content in the head and neck squamous cell cancer cell line after 48 h of incubation; however, the reactivity was restricted to the adherent junctions. At increasing concentrations of sulindac sulfone, intercellular E-Cadherin immunostaining intensified. ELISA also depicted significant rising levels of E-Cadherin. Sulindac sulfone contributes to the inactivation of cGMP phosphodiesterase. Thus, the accumulation of cellular cGMP and protein kinase G is induced. The following degradation of the phosphorylated β-catenin and the dissociation from the Cadherin-catenin complex releases E-Cadherin. This may also contribute to growth inhibition and coordinate with apoptosis induction. It is not really clear as to, which pathway results in the elevation of the E-Cadherin proteins. However, in epithelial cancer cells, the Cadherin-catenin complex serves as a target for the chemopreventive agent, sulindac sulfone.

Oncology 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

Singh, Tripti published the artcileNitric oxide donor exisulind is an effective inhibitor of murine photocarcinogenesis, Computed Properties of 59973-80-7, the publication is Photochemistry and Photobiology (2012), 88(5), 1141-1148, database is CAplus and MEDLINE.

NO-releasing nonsteroidal anti-inflammatory drugs (NO-NSA-IDs) have been shown to have anti-inflammatory, antiproliferative and apoptosis-inducing effects in tumor cells. Herein, we have investigated the effects of NO-exisulind on the growth of UVB-induced skin tumor development in a murine model. We found that the topical treatment with NO-exisulind significantly reduced UVB-induced tumors in SKH-1 hairless mice. The tumors/tumor bearing mouse, the number of tumors/mouse and tumor volume/mouse decreased significantly (P < 0.05) as compared with vehicle-treated and UVB-irradiated pos. controls. Consistently, NO-exisulind-treated animals showed reduced expression of proliferation markers, such as PCNA and cyclin D1. These mice also manifested increased expression of proapoptotic Bax and decreased expression of antiapoptotic Bcl2 with an increase in the number of TUNEL-pos. cells in tumors. We also investigated whether NO-exisulind-treated tumors are less invasive and progress less efficiently from benign to malignant carcinomas. For this, tumors were stained for various epithelial-mesenchymal transition (EMT) markers. NO-exisulind decreased the expression of mesenchymal markers, such as Fibronectin, N-cadherin, SNAI, Slug and Twist and enhanced the epithelial marker E-cadherin. Similarly, UVB-induced phosphorylation of Erk1/2 and p38 was decreased in NO-exisulind-treated animals. These data suggest that NO-exisulind reduces tumor growth and inhibits tumor progression by blocking proliferation, inducing apoptosis and reducing EMT.

Photochemistry and Photobiology 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 C11H10O3, Computed Properties of 59973-80-7.

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

Tai, Hsin-Hsiung published the artcileRegulation of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) by non-steroidal anti-inflammatory drugs (NSAIDs), Computed Properties of 59973-80-7, the publication is Prostaglandins & Other Lipid Mediators (2011), 96(1-4), 37-40, database is CAplus and MEDLINE.

A review. NSAIDs are known to be inhibitors of cyclooxygenase-2 (COX-2) accounting for their anti-inflammatory and anti-tumor activities. However, the anti-tumor activity cannot be totally attributed to their COX-2 inhibitory activity as these drugs can also inhibit the growth and tumor formation of COX-2-null cell lines. Several potential targets aside from COX-2 for NSAIDs have been proposed. 15-Hydroxyprostaglandin dehydrogenase (15-PGDH), a key prostaglandin catabolic enzyme, was recently shown to be a tumor suppressor. Effects of NSAIDs on 15-PGDH expression were therefore studied. Flurbiprofen, indomethacin and other NSAIDs stimulated 15-PGDH activity in colon cancer HT29 cells as well as in lung cancer A549 cells and glioblastoma T98G cells. (R)-flurbiprofen and sulindac sulfone, COX-2 inactive analogs, also stimulated 15-PGDH activity indicating induction of 15-PGDH is independent of COX-2 inhibition. Stimulation of 15-PGDH expression and activity by NSAIDs was examined in detail in colon cancer HT29 cells using flurbiprofen as a stimulant. Flurbiprofen stimulated 15-PGDH expression and activity by increasing transcription and translation and by decreasing the turnover of 15-PGDH. Mechanism of stimulation of 15-PGDH expression is not clear. Protease(s) involved in the turnover of 15-PGDH remains to be identified. However, flurbiprofen down-regulated matrix metalloproteinase-9 (MMP-9) which was shown to degrade 15-PGDH, but up-regulated tissue inhibitor of metalloproteinase-1 (TIMP-1), an inhibitor of MMP-9 contributing further to a slower turnover of 15-PGDH. Taken together, NSAIDs may up-regulate 15-PGDH by increasing the protein expression as well as decreasing the turnover of 15-PGDH in cancer cells.

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 C10H16Br3N, Computed Properties of 59973-80-7.

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

Jia, Zhongjiang published the artcileDetermination of drug-polymer binding constants by affinity capillary electrophoresis for aryl propionic acid derivatives and related compounds, Name: Sulindac sulfone, the publication is Journal of Pharmaceutical Sciences (2013), 102(3), 960-966, database is CAplus and MEDLINE.

The binding constants (K_bs) of 17 aryl propionic acid derivatives (APADs) and related compounds with polyvinylpyrrolidone (PVP K30) and vinylpyrrolidone-vinyl acetate copolymer (Kollidon VA64) in aqueous media were determined by affinity capillary electrophoreses (ACE). The K_bs of APAD to polymers increase with octanol-water partition coefficients of the compounds Kollidon VA64 is a stronger binder than PVP K30 to APAD compounds The K_bs are greater at pH 4 than at pH 9. Both hydrophobic interaction and hydrogen bonding may be involved. However, hydrophobic interaction appears to be dominant. The ACE method is simple and fast, which could be used to study drug-polymer interaction in aqueous media. © 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci.

Journal of Pharmaceutical Sciences 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

Allsup, Jodie published the artcileApplicability domain of the GADD45a reporter assays: non-steroidal anti-inflammatory drugs do not produce misleading genotoxicity results, SDS of cas: 59973-80-7, the publication is Toxicology Research (Cambridge, United Kingdom) (2013), 2(5), 343-351, database is CAplus.

Increased expression of the GADD45a gene is a very specific biomarker of genotoxin exposure in TK6 cells, and has been exploited in green fluorescent protein and luciferase reporter genotoxicity assays. A recent European Food Safety Authority suggested that the GADD45a-reporter genotoxicity assays might produce misleading pos. results for non-steroidal anti-inflammatory drugs. This study was conceived to test the hypothesis that these drugs should be excluded from the applicability domain of the TK6 cell GADD45a GreenScreen HC and BlueScreen HC reporter assays. Data from published screening and validation studies have been reviewed, and new test data have been generated from 20 NSAIDS, from both reporter assays, both in the presence and absence of metabolic activation. The data fail to support this hypothesis: the high specificity of the GADD45a reporter assays is maintained amongst NSAIDs.

Toxicology Research (Cambridge, United Kingdom) 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

Krier, Fabrice published the artcileOptimisation and validation of a fast HPLC method for the quantification of sulindac and its related impurities, Category: naphthyridine, the publication is Journal of Pharmaceutical and Biomedical Analysis (2011), 54(4), 694-700, database is CAplus and MEDLINE.

The European Pharmacopoeia describes a liquid chromatog. (LC) method for the quantification of sulindac, using a quaternary mobile phase including chloroform and with a rather long run time. In the present study, a new method using a short sub-2 μm column, which can be used on a classical HPLC system, was developed. The new LC conditions (without chloroform) were optimized by means of a new methodol. based on design of experiments in order to obtain an optimal separation Four factors were studied: the duration of the initial isocratic step, the percentage of organic modifier at the beginning of the gradient, the percentage of organic modifier at the end of the gradient and the gradient time. The optimal condition allows the separation of sulindac and of its 3 related impurities in 6 min instead of 18 min. Finally, the method was successfully validated using an accuracy profile approach in order to demonstrate its ability to accurately quantify these compounds

Journal of Pharmaceutical and Biomedical 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, Category: naphthyridine.

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

Bouchard, Geraldine published the artcileLipophilicity and solvation of anionic drugs, COA of Formula: C20H17FO4S, the publication is Chemistry – A European Journal (2002), 8(15), 3478-3484, database is CAplus and MEDLINE.

This paper first gives a brief review of the main techniques used to measure the lipophilicity of neutral and ionic drugs, namely the shake-flask method, potentiometry, and cyclic voltammetry at liquid-liquid interfaces. The lipophilicity of 28 acidic compounds with various functional groups was studied by potentiometry and cyclic voltammetry in the n-octanol/water and 1,2-dichloroethane/water systems in order to complement our understanding of the lipophilicity of neutral and ionized acids and to clarify the solvation mechanisms responsible for their partition. The parameter diff(log P_dce^N-A) (i.e., log P of the neutral acid minus standard log P of the conjugated anion in 1,2-dichloroethane/water) was shown to depend not only on intramol. interactions and conformational effects in the neutral and anionic forms, but also on the delocalization of the neg. charge in the anion, confirming the ability of Born’s solvation model to describe qual. the effect of the mol. radius on the lipophilicity of ions.

Chemistry – A European 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, COA of Formula: C20H17FO4S.

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