Tag: M.W=350-400

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 artcileP38MAPK inhibitor SB203580 sensitizes human SNU-C4 colon cancer cells to exisulind-induced apoptosis, Application In Synthesis of 59973-80-7, the publication is Oncology Reports (2006), 16(5), 1131-1135, database is CAplus and MEDLINE.

Sulindac sulfone (exisulind), is a promising anti-cancer agent because of its ability to induce apoptosis in a variety of malignant cell types and its minimal toxicity to normal cells. The induction of apoptosis is thought to account for the growth inhibitory effect of exisulind. The mitogen-activated protein kinase (MAPK) cascade has been implicated in the regulation of apoptosis in response to exisulind. With human SNU-C4 colon cancer cells that were much more resistant to exisulind than other colon cancer cells, in this study, we investigated whether the modulation of MAPK activity by using selective MAPK inhibitors can contribute to sensitizing SNU-C4 cells to exisulind. Exisulind (400 and 600 渭M) slightly increased the phosphorylation of pERK1/2 but pretreatment with the pERK1/2 inhibitor PD98059 did not significantly change the apoptotic response of SNU-C4 cells. The same doses of exisulind increased the phosphorylation of p38MAPK, and pretreatment with the p38MAPK inhibitor SB203580 significantly potentiated growth inhibition and apoptosis induced by exisulind in SNU-C4 cells. We further found that apoptosis induced by a combination of exisulind and SB203580 was mediated through caspase activation. Collectively, our findings indicate that selective p38MAPK inhibitors potentiate apoptosis induction by exisulind in SNU-C4 cells. Such combinations may provide a more effective and less toxic strategy for the prevention or treatment of colon cancer.

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, Application In Synthesis of 59973-80-7.

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

Sfoungaristos, Stavros published the artcileNeoadjuvant chemotherapy prior to radical prostatectomy for patients with high-risk prostate cancer: a systematic review, Synthetic Route of 59973-80-7, the publication is Chemotherapy Research and Practice (2013), 386809, 7 pp., database is CAplus and MEDLINE.

High-risk prostate cancer represents a pretentious clin. problem since a significant number of its patients will relapse and progress after radical prostatectomy. Neoadjuvant chemotherapy may be valuable since its efficacy in hormone-resistant prostate cancer has been established. In this paper, we report studies of neoadjuvant chemotherapies that have been used in high-risk patients prior to radical prostatectomy. Even though the results regarding the prognostic surrogates are not significant, the effects on clin. and pathol. outcomes are promising, while toxicity in most of the studies is in the expected field.

Chemotherapy Research and Practice 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 C42H63O3P, Synthetic Route of 59973-80-7.

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

Pangburn, Heather A. published the artcileSulindac metabolites inhibit epidermal growth factor receptor activation and expression, Related Products of naphthyridine, the publication is Journal of Carcinogenesis (2005), No pp. given, database is CAplus and MEDLINE.

Background: Regular use of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with a decreased mortality from colorectal cancer (CRC). NSAIDs induce apoptotic cell death in colon cancer cells in vitro and inhibit growth of neoplastic colonic mucosa in vivo however, the biochem. mechanisms required for these growth inhibitory effects are not well defined. We previously reported that metabolites of the NSAID sulindac downregulate extracellular-signal regulated kinase 1/2 (ERK1/2) signaling and that this effect is both necessary and sufficient for the apoptotic effects of these drugs. The goal of this project was to specifically test the hypothesis that sulindac metabolites block activation and/or expression of the epidermal growth factor (EGF) receptor (EGFR). Methods: HT29 human colon cancer cells were treated with EGF, alone, or in the presence of sulindac sulfide or sulindac sulfone. Cells lysates were assayed by immunoblotting for phosphorylated EGFR (pEGFR, pY1068), total EGFR, phosphorylated ERK1/2 (pERK1/2), total ERK1/2, activated caspase-3, and 伪-tubulin. Results: EGF treatment rapidly induced phosphorylation of both EGFR and ERK1/2 in HT29 colon cancer cells. Pretreatment with sulindac metabolites for 24h blocked EGF-induced phosphorylation of both EGFR and ERK1/2 and decreased total EGFR protein expression. Under basal conditions, downregulation of pEGFR and total EGFR was detected as early as 12h following sulindac sulfide treatment and persisted through at least 48h. Sulindac sulfone induced downregulation of pEGFR and total EGFR was detected as early as 1h and 24h, resp., following drug treatment, and persisted through at least 72h. EGFR downregulation by sulindac metabolites was observed in three different CRC cell lines, occurred prior to the observed downregulation of pERK1/2 and induction of apoptosis by these drugs, and was not dependent of caspase activation. Conclusion: These results suggest that downregulation of EGFR signaling by sulindac metabolites may occur, at least in part, by inhibiting activation and expression of EGFR. Inhibition of EGFR signaling may account for part of the growth inhibitory and chemopreventive effects of these compounds

Journal of Carcinogenesis 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

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

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