InChI=1S/C13H18N2O5S/c1- 21(18,19)14-12-8-7-10(15(16)17)9-13(12)20-11-5-3-2-4-6-11/h7-9,11,14H,2-6H2,1H3 |
| KTDZCOWXCWUPEO-UHFFFAOYSA-N |
| CS(=O)(=O)Nc1ccc(cc1OC1CCCCC1)[N+]([O-])=O |
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cyclooxygenase 2 inhibitor
A cyclooxygenase inhibitor that interferes with the action of cyclooxygenase 2.
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antineoplastic agent
A substance that inhibits or prevents the proliferation of neoplasms.
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View more via ChEBI Ontology
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N-[2-(cyclohexyloxy)-4-nitrophenyl]methanesulfonamide
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N-(2-Cyclohexyloxy-4-nitrophenyl)methanesulfonamide
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ChemIDplus
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NS 398
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ChemIDplus
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NS398
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ChemIDplus
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123653-11-2
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CAS Registry Number
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ChemIDplus
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6611485
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Reaxys Registry Number
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Reaxys
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Bono F, De Smet F, Herbert C, De Bock K, Georgiadou M, Fons P, Tjwa M, Alcouffe C, Ny A, Bianciotto M, Jonckx B, Murakami M, Lanahan AA, Michielsen C, Sibrac D, Dol-Gleizes F, Mazzone M, Zacchigna S, Herault JP, Fischer C, Rigon P, Ruiz de Almodovar C, Claes F, Blanc I, Poesen K, Zhang J, Segura I, Gueguen G, Bordes MF, Lambrechts D, Broussy R, van de Wouwer M, Michaux C, Shimada T, Jean I, Blacher S, Noel A, Motte P, Rom E, Rakic JM, Katsuma S, Schaeffer P, Yayon A, Van Schepdael A, Schwalbe H, Gervasio FL, Carmeliet G, Rozensky J, Dewerchin M, Simons M, Christopoulos A, Herbert JM, Carmeliet P (2013)
Inhibition of tumor angiogenesis and growth by a small-molecule multi-FGF receptor blocker with allosteric properties.
Cancer cell 23, 477-488 [PubMed:23597562]
[show Abstract]
Receptor tyrosine kinases (RTK) are targets for anticancer drug development. To date, only RTK inhibitors that block orthosteric binding of ligands and substrates have been developed. Here, we report the pharmacologic characterization of the chemical SSR128129E (SSR), which inhibits fibroblast growth factor receptor (FGFR) signaling by binding to the extracellular FGFR domain without affecting orthosteric FGF binding. SSR exhibits allosteric properties, including probe dependence, signaling bias, and ceiling effects. Inhibition by SSR is highly conserved throughout the animal kingdom. Oral delivery of SSR inhibits arthritis and tumors that are relatively refractory to anti-vascular endothelial growth factor receptor-2 antibodies. Thus, orally-active extracellularly acting small-molecule modulators of RTKs with allosteric properties can be developed and may offer opportunities to improve anticancer treatment. | Ke X, Dou F, Cheng Z, Dai H, Zhang W, Qu X, Ding P, Zuo X (2013)
High expression of cyclooxygenase-2 in uterine fibroids and its correlation with cell proliferation.
European journal of obstetrics, gynecology, and reproductive biology 168, 199-203 [PubMed:23398724]
[show Abstract]
ObjectiveTo investigate the expression of cyclooxygenase-2 (COX-2) in uterine fibroids and healthy uterine smooth muscle as well as its role in the pathogenesis of uterine fibroids.MethodsWe collected uterine fibroid tissues and their paired adjacent healthy uterine smooth muscle tissues from 30 cases of uterine fibroids. We used immunohistochemistry and quantitative real-time PCR, as well as western blot to detect COX-2 expression. Using the COX-2 inhibitors NS-398 and celecoxib, we observed the response to the inhibitors in the healthy and fibroid smooth muscle cell pairs.ResultsCOX-2 was detected by immunohistochemistry in both uterine fibroids and uterine smooth muscle, with higher immunoreactivity in uterine fibroids; the positive index of the smooth muscle cells was 11.90 and the positive index of uterine fibroids cells was 46.50 (P<0.05). The expression of COX-2 mRNA in uterine fibroids was higher (0.122±0.062) than in normal smooth muscle tissue (0.025±0.009; P<0.05). Also, the western blot results showed that COX-2 expression was significantly higher in uterine fibroid cases, as compared to the expression in uterine smooth muscle. Immunofluorescence showed that the occurrence of COX-2 was obviously higher in smooth muscle cells of uterine fibroids than in the healthy smooth muscle cells. NS-398 or celecoxib significantly inhibited the proliferation of smooth muscle cells of uterine fibroids, but did not inhibit the proliferation of healthy smooth muscle cells. Accordingly, NS-398 or celecoxib significantly reduced the expression of the downstream metabolite of COX-2, PGE2, in the smooth muscle cells of uterine fibroids, but not in healthy smooth muscle cells.ConclusionCOX-2 expression in uterine fibroids was significantly higher than in healthy uterine smooth muscles. The inhibition of COX-2 activity significantly reduced the proliferation of smooth muscle cells of the uterine fibroids, suggesting that COX-2 plays an important role in the pathogenesis of uterine fibroids. | Abraki SB, Khalaj L, Shaerzadeh F, Khodagholi F (2013)
Simultaneous inhibition of COX-2 and activation of PPAR-γ resulted in the same level and pattern of neuroprotection as they were targeted separately.
Journal of molecular neuroscience : MN 49, 116-129 [PubMed:23132402]
[show Abstract]
The inflammatory response is an immune response of the body when exposed to internal and external stimuli. Cyclooxygenases (COX) are major inflammatory mediators implicated in inflammation. COX-2 is reported to be involved in neuroinflammation. Moreover, 15-Deoxy-D (12,14)-prostaglandin J2 (15d-PGJ2), an endogenous ligand of peroxisome proliferator-activated receptor gamma (PPAR-γ), has been demonstrated to have anti-inflammatory actions. In this study, we investigated whether co-therapy of a selective COX-2 inhibitor NS-398 and 15d-PGJ2 as a PPAR-γ ligand could exert additional neuroprotective effects in rat pheochromocytoma (PC12) cells. Our findings showed that 15d-PGJ2 and NS-398 suppress the apoptotic pathway in PC12 cells exposed to H(2)O(2) by attenuation of the Bax/Bcl-2 ratio. This effect was mediated through PPAR-γ, as it was reversed by GW9662 (a PPAR-γ inhibitor). Also, 15d-PGJ2 and NS-398 induced the Nrf2 signaling pathway and decreased NF-κB level in a PPAR-γ-dependent manner. We found that coadministration of a selective COX-2 inhibitor and a PPAR-γ ligand in PC12 cells has equal neuroprotective effect compared to their effects when used separately. Considering the higher affinity of 15d-PGJ2 for PPAR-γ than NS-398, it seems that the observed neuroprotection of this combination therapy was from 15d-PGJ2. | Que W, Li S, Chen J (2013)
NS-398 enhances the efficacy of bortezomib against RPMI8226 human multiple myeloma cells.
Molecular medicine reports 7, 1641-1645 [PubMed:23545701]
[show Abstract]
Bortezomib is commonly used in treating multiple myeloma (MM). However, a number of patients develop resistance to bortezomib over time. Cox-2 is overexpressed in MM cells and contributes to apoptosis resistance and MM development. In the present study, RPMI8226 MM cells were treated with the Cox-2 inhibitor NS-398 to investigate whether it enhanced the effect of bortezomib on MM. The results showed that NS-398 and bortezomib acted synergistically to inhibit growth, arrest the cell cycle at the G1 phase and to induce the apoptosis of MM cells. NS-398 inhibited the NF-κB p65 protein levels and the expression of various NF-κB target genes, including cyclin D1, c-Myc, survivin and Bcl-2. In conclusion, NS-398 enhanced the efficacy of bortezomib against MM cells in vitro and this was associated with the inhibition of NF-κB signaling. These findings suggest that the combined use of NS-398 and bortezomib may constitute a promising novel treatment protocol for MM patients. | Sugiyama T, Meakin LB, Galea GL, Lanyon LE, Price JS (2013)
The cyclooxygenase-2 selective inhibitor NS-398 does not influence trabecular or cortical bone gain resulting from repeated mechanical loading in female mice.
Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA 24, 383-388 [PubMed:22349912]
[show Abstract]
UnlabelledA single injection of the cyclooxygenase-2 (COX-2) selective inhibitor NS-398 reduces bone's osteogenic response to a single period of mechanical loading in female rats, while women taking COX-2 selective inhibitors do not have lower bone mass. We show that daily NS-398 injection does not influence bone gain from repeated loading in female mice.IntroductionProstaglandins are mediators of bone cells' early response to mechanical stimulation. COX-2 expression is up-regulated by exposure of these cells to mechanical strain or fluid flow, and the osteogenic response to a single loading period is reduced by COX-2 inhibition. This study determined, in female mice in vivo, the effect of longer term COX-2 inhibition on adaptive (re)modelling of cortical and trabecular bone in response to repeated loading.MethodsNineteen-week-old female C57BL/6 mice were injected with vehicle or NS-398 (5 mg/kg/day) 5 days a week for 2 weeks. On three alternate days each week, the right tibiae/fibulae were axially loaded [40 cycles (7 min)/day] three hours after injection. Left limbs acted as internal controls. Changes in three-dimensional bone architecture were analysed by high-resolution micro-computed tomography.ResultsIn control limbs NS-398 was associated with reduced trabecular number but had no influence on cortical bone. In loaded limbs trabecular thickness and cortical periosteally enclosed volume increased. NS-398 showed no effect on this response.ConclusionPharmacological inhibition of COX-2 by NS-398 does not affect trabecular or cortical bone's response to repeated mechanical loading in female mice and thus would not be expected to impair the functional adaptation of bone to physical activity in women. | Wang X, Liang Y, Wang J, Wang M (2013)
Effect of NS-398, a cyclooxygenase-2 selective inhibitor, on the cytotoxicity of cytotoxic T lymphocytes to ovarian carcinoma cells.
Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 34, 1517-1522 [PubMed:23456767]
[show Abstract]
Cyclooxygenase-2 (COX-2) is a key limited enzyme of prostaglandin (PG) synthesis and has been demonstrated to be overexpressed in cancer. N-[2-(cyclohexyloxy)-4-nitropheny]-methane sulfonamide (NS-398) is a special inhibitor of COX-2 and may suppress PGE2 release and promote immune response mechanism of cytotoxic T lymphocytes (CTLs). We aimed to investigate the effect of NS-398 on the PGE2 release, proliferation of ovarian carcinoma cell line CAOV3, and immune cytotoxicity of CTLs. CAOV3 cells were incubated with 0, 50, and 100 μmol/L NS-398 for 24, 48, and 72 h. Cell viability was determined by trypan blue staining. PGE2 was measured using radioimmunoassay. CTLs were generated from peripheral blood mononuclear cells after stimulated by CAOV3 cells or CAOV3 cells treated with NS-398 when IL-2 existed. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was used to evaluate the cytotoxicity of CTLs. As expected, the amount, cell density, cellular volume, and growth speed of CAOV3 cells incubated with NS-398 were significantly decreased compared with control group. This difference became more obvious with an increase in the NS-398 concentration and incubation time. Similarly, PGE2 released from CAOV3 cells treated with 50 and 100 μmol/L NS-398 was significantly decreased compared with control group (P<0.05). There was also significance in PGE2 between the two groups treated with 50 and 100 μmol/L NS-398 (P<0.05). Compared with control group, the killing rates of CTLs to CAOV3 treated with 50 and 100 μmol/L NS-398 were significantly increased (P<0.05). However, there is no significant difference between them. Together, our results suggest that NS-398 could be useful in prevention and therapy of ovarian carcinoma. |
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