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SC-1

(Synonyms: 1-(4-Chloro-3-(trifluoromethyl)phenyl)-3-(4-(4-cyanophenoxy)phenyl)urea, STAT3-IN-7) 目录号 : GC25899

SC-1 (1-(4-Chloro-3-(trifluoromethyl)phenyl)-3-(4-(4-cyanophenoxy)phenyl)urea, STAT3-IN-7), a Sorafenib analogue and potently inhibits the phosphorylation of STAT3, induces cell apoptosis through SHP-1 dependent STAT3 inactivation.

SC-1 Chemical Structure

Cas No.:1313019-65-6

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产品描述

SC-1 (1-(4-Chloro-3-(trifluoromethyl)phenyl)-3-(4-(4-cyanophenoxy)phenyl)urea, STAT3-IN-7), a Sorafenib analogue and potently inhibits the phosphorylation of STAT3, induces cell apoptosis through SHP-1 dependent STAT3 inactivation.

[1] Liu CY, et al. Breast Cancer Res. 2013;15(4):R63.

Chemical Properties

Cas No. 1313019-65-6 SDF Download SDF
别名 1-(4-Chloro-3-(trifluoromethyl)phenyl)-3-(4-(4-cyanophenoxy)phenyl)urea, STAT3-IN-7
分子式 C21H13ClF3N3O2 分子量 431.8
溶解度 DMSO: 86 mg/mL (199.17 mM);Water: Insoluble;Ethanol: 86 mg/mL (199.17 mM) 储存条件 Store at -20°C
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1 mM 2.3159 mL 11.5794 mL 23.1589 mL
5 mM 0.4632 mL 2.3159 mL 4.6318 mL
10 mM 0.2316 mL 1.1579 mL 2.3159 mL
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Research Update

SC-1, a sorafenib derivative, shows anti-tumor effects in osteogenic sarcoma cells

J Orthop Res 2013 Feb;31(2):335-42.PMID:22926753DOI:10.1002/jor.22218.

Despite significant advances in the treatment of osteosarcoma (OS), overall survival rate of OS patients has remained relatively constant for over two decades and novel approaches are needed to further improve prognosis. Here, we report the anti-tumor effect of SC-1, a novel sorafenib derivative that closely resembles sorafenib structurally but is devoid of kinase inhibitory activity, on OS cells through mediation of signal transducer and activator of transcription 3 (STAT3). SC-1 showed similar effects to sorafenib on growth inhibition and apoptosis, and downregulated phospho-STAT3 (p-STAT3) at tyrosine 705 in all tested OS cell lines (U2OS, HOS, and 143B). Expression of STAT3-driven genes, including cylcin D1 and c-myc, were also repressed by SC-1. Ectopic expression of STAT3 in 143B cells abolished apoptosis in SC-1-treated cells. Inhibition of SHP-1 decreased SC-1-induced apoptosis. SC-1 upregulated the activity of SHP-1 in tested OS cell lines in a dose-dependent manner. Finally, SC-1 reduced 143B tumor growth significantly in vivo, which was associated with downregulation of p-STAT3 and upregulation of SHP-1 activity. These data demonstrate that SC-1 has clinical potential for the treatment of OS patients.

Production, biodistribution, and dosimetry of (47)SC-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethylene phosphonic acid as a bone-seeking radiopharmaceutical

J Med Phys 2015 Jul-Sep;40(3):156-64.PMID:26500402DOI:10.4103/0971-6203.165078.

In this study 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethylene phosphonic acid (DOTMP) was used as the polyaminophosphonic acid carrier ligand and the therapeutic potential of the bone seeking radiopharmaceutical (47)Sc-DOTMP was assessed by measuring its dosage-dependent skeletal uptake and then the absorbed radiation dose of human organs was estimated. Because of limited availability of (47)Sc we performed some preliminary studies using (46)Sc. (46)Sc was produced with a specific activity of 116.58 MBq/mg (3.15 mCi/mg) and radionuclide purity of 98%. (46)Sc-DOTMP was prepared and an activity of 1.258 MBq (34 μCi) at a chelant-to-metal ratio of 60:1 was administered to five groups of mice with each group containing 3 mice that were euthanized at 4, 24, 48, 96 and 192 h post administration. The heart, lungs, liver, spleen, kidneys, intestine, skin, muscle, and a femur were excised, weighed, and counted. The data were analyzed to determine skeletal uptake and source organ residence times and cumulated activities for (47)Sc-DOTMP. (46)Sc-DOTMP complex was prepared in radiochemical purity about 93%. In vitro stability of complex was evaluated at room temperature for 48 h. Biodistribution studies of complex in mice were studied for 7 days. The data were analyzed to estimate skeletal uptake and absorbed radiation dose of human organs using biodistribution data from mice. By considering the results, (47)Sc-DOTMP is a possible therapeutic agent for using in palliation of bone pain due to metastatic skeletal lesions from several types of primary cancers in prostate, breast, etc.

SC-1, an antimycotic spirostan saponin from Solanum chrysotrichum

Planta Med 2001 Jun;67(4):372-4.PMID:11458462DOI:10.1055/s-2001-14332.

A new antimycotic steroidal saponin named SC-1 has been isolated from the leaves of Solanum chrysotrichum by bioassay-guided fractionation. The structure of SC-1 was characterized as 3-O-[beta-quinovopyranosyl(1-->6)-beta-glucopyranosyl(1-->6)-beta- glucopyranosyl]chlorogenin on the basis of spectral analyses and chemical evidence.

Sorafenib and its derivative SC-1 exhibit antifibrotic effects through signal transducer and activator of transcription 3 inhibition

Proc Natl Acad Sci U S A 2015 Jun 9;112(23):7243-8.PMID:26039995DOI:10.1073/pnas.1507499112.

Signal transducer and activator of transcription 3 (STAT3) had been involved in liver fibrogenesis. We aimed to explore the antifibrotic activities of sorafenib and its derivative SC-1 (devoid of Raf kinase inhibition activity) both in vivo and in vitro with special focus on the STAT3 pathway in hepatic stellate cells (HSCs). The clinical role of STAT3 in chronic hepatitis B (CHB) was also investigated. Experimental fibrosis mouse models were established by thioacetamide injection and bile duct ligation in Balb/C mice and treated with sorafenib and SC-1. Rat and human HSCs were used for mechanistic investigations. Forty CHB patients were enrolled to quantify the hepatic phospho-STAT3 (p-STAT3) levels and correlated with liver fibrosis. Both sorafenib and SC-1 ameliorated liver fibrosis in vivo and promoted HSC apoptosis in vitro. p-STAT3 and downstream signals were down-regulated after sorafenib and SC-1 treatment in HSC. STAT3 overexpression in HSC enhanced cell proliferation and undermined the apoptotic effects of sorafenib and SC-1, whereas STAT3-specific inhibition promoted HSC apoptosis. Sorafenib and SC-1 activated Src-homology protein tyrosine phosphatase-1 (SHP-1) and STAT3 inhibition followed. Of particular interest, in CHB patients with advanced liver fibrosis, p-STAT3 in HSC was significantly overexpressed and positively correlated with the severity of liver fibrosis and plasma IL-6 levels. In conclusion, sorafenib and SC-1 ameliorate liver fibrosis through STAT3 inhibition in HSC and STAT3 may potentially serve as a promising fibrotic biomarker and target in liver fibrosis. SHP-1 phosphatase-directed STAT3 inhibition may represent a previously unidentified strategy for antifibrotic drug discovery.

Simultaneous degradation of cypermethrin and its metabolite, 3-phenoxybenzoic acid, by the cooperation of Bacillus licheniformis B-1 and sphingomonas sp. SC-1

J Agric Food Chem 2014 Aug 20;62(33):8256-62.PMID:25068244DOI:10.1021/jf502835n.

Cypermethrin (CY) and its metabolite, 3-phenoxybenzoic acid (3-PBA), generally coexist in agricultural soil and cause a toxic effect on the human body. In this study, CY and its metabolite 3-PBA were simultaneously degraded by the cooperation of Bacillus licheniformis B-1 and Sphingomonas sp. SC-1. The effects of the inoculation proportion and inoculation method of these two strains, cultivation time, and initial CY content on the degradation of CY and 3-PBA were investigated. Furthermore, the degradation of CY and 3-PBA in soil environment by using the cooperation of these two strains was also determined. When the inoculation proportion of the biomass of strain B-1/strain SC-1 was 3.3:6.7, strain B-1 was inoculated first, and strain SC-1 was inoculated after 24 h of cultivation, 75.60% CY (100 mg L(-1)) was degraded at 72 h and the 3-PBA content was 10.31 mg L(-1). Compared with those by using only strain B-1, the half-life of CY by using these two strains was shortened from 71.90 to 35.71 h, and the yield coefficient of 3-PBA was decreased from 0.8938 to 0.2651. As in the soil environment, the CY content by using these two strains within a period of 25 days declined from 22.71 to 5.33 mg kg(-1) and the 3-PBA content was 1.84 mg kg(-1). Compared with those by using only strain B-1, the half-life of CY by using these two strains was shortened from 19.86 to 11.34 days and the yield coefficient of 3-PBA was decreased from 0.5302 to 0.2056. This work could develop a promising approach for the simultaneous degradation of CY and its metabolite 3-PBA in agricultural soil.