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NSC745885 Sale

目录号 : GC61142

NSC745885是一种有效的抗肿瘤(anti-tumor)试剂,对多种癌细胞株有选择性毒性,但对正常细胞没有毒性。NSC745885是一种有效的EZH2的下调因子通过蛋白酶体降解途径。NSC745885为晚期膀胱癌和口腔鳞癌的研究提供了可能性。

NSC745885 Chemical Structure

Cas No.:4219-52-7

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5mg
¥2,250.00
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10mg
¥4,050.00
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50mg
¥11,700.00
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100mg
¥16,200.00
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产品描述

NSC745885 an effective anti-tumor agent, shows selective toxicity against multiple cancer cell lines but not normal cells. NSC745885 is an effective down-regulator of EZH2 via proteasome-mediated degradation. NSC745885 provides possibilities for the study of advanced bladder and oral squamous cell carcinoma (OSCC) cancers[1][2].

NSC745885 (0.5-4 μM; 24, 48 or 72 hours) has a growth inhibitory or death-promoting effect on the SAS cells, it significantly decreases the densities of cultured cells when compared with untreated cells. The IC50 of NSC745885 is 0.85 μM after 72 hours' treatment[1].NSC745885 (0.5-4 μM; 24 hours) increases annexin V positive cells in a dose-dependent manner, and the differences appears as a dose-dependent manner[1].NSC745885 (0.5-2 μM; 24 or 48 hours) decreases XIAP protein levels and increases protein levels both as a dose-dependent manner in SAS cells[1]. Cell Viability Assay[1] Cell Line: SAS cells is obtained from a poorly differentiated human squamous cell carcinoma

NSC745885 (intraperitoneal injection; 2 mg/kg; once daily; 10 days) treatment significantly reduces tumor size when compared with the vehicle control, and exhibits a higher safety than doxorubicin[1]. Animal Model: Eight-week-old NOD/SCID (NOD.CB17 Prkdcscid/J) mice[1]

[1]. Chen YW, et al.A novel compound NSC745885 exerts an anti-tumor effect on tongue cancer SAS cells in vitro and in vivo.PLoS One. 2014 Aug 15;9(8):e104703. [2]. Tang SH, et al. Pharmacologic down-regulation of EZH2 suppresses bladder cancer in vitro and in vivo.Oncotarget. 2014 Nov 15;5(21):10342-55.

Chemical Properties

Cas No. 4219-52-7 SDF
Canonical SMILES O=C(C1=C(C2=O)C3=NSN=C3C=C1)C4=C2C=CC=C4
分子式 C14H6N2O2S 分子量 266.27
溶解度 DMSO: < 1 mg/mL (insoluble or slightly soluble) *NSC745885 is usually formulated as a suspension. 储存条件 Store at -20°C
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储备液的保存方式和期限:-80°C 储存时,请在 6 个月内使用,-20°C 储存时,请在 1 个月内使用。
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溶解性数据

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1 mM 3.7556 mL 18.7779 mL 37.5559 mL
5 mM 0.7511 mL 3.7556 mL 7.5112 mL
10 mM 0.3756 mL 1.8778 mL 3.7556 mL
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Research Update

A novel compound NSC745885 exerts an anti-tumor effect on tongue cancer SAS cells in vitro and in vivo

PLoS One 2014 Aug 15;9(8):e104703.PMID:25127132DOI:10.1371/journal.pone.0104703.

Objective: Oral squamous cell carcinoma (OSCC) is a prevalent cancer, especially in developing countries. Anthracyclines and their anthraquinone derivatives, such as doxorubicin, exhibit a cell growth inhibitory effect and have been used as anti-cancer drugs for many years. However, the cardiotoxicity of anthracycline antibiotics is a major concern in their clinical application. NSC745885 is a novel compound synthesized from 1,2-diaminoanthraquinone, which subsequently reacts with thionyl chloride and triethylamine. The present study aimed to investigate the anti-oral cancer potential and the safety of NSC745885. Methods: We investigated the anti-cancer potential of NSC745885 in oral squamous carcinoma cell lines and in an in vivo oral cancer xenograft mouse model. The expression of apoptotic related genes were evaluated by real-time RT-PCR and western bloting, and the in vivo assessment of apoptotic marker were measured by immunohistochemical staining. The anti-tumor efficiency and safety between doxorubicin and NSC745885 were also compared. Results: Our results demonstrated that NSC745885 exhibits anti-oral cancer activity through the induction of apoptosis in cancer cells and in tumor-bearing mice, and this treatment did not induce marked toxicity in experimental mice. This compound also exhibits a comparable anti-tumor efficiency and a higher safety in experimental mice when compared to doxorubicin. Conclusions: The data of this study provide evidence for NSC745885 as a potential novel therapeutic drug for the treatment of human OSCC.

Pharmacologic down-regulation of EZH2 suppresses bladder cancer in vitro and in vivo

Oncotarget 2014 Nov 15;5(21):10342-55.PMID:25431950DOI:10.18632/oncotarget.1867.

The polycomb group gene, EZH2, is highly expressed in advanced bladder cancer. Here we demonstrated that down-regulation of EZH2 in tumor tissues after neo-adjuvant chemotherapy correlated with good therapeutic response in advanced bladder cancer. We next developed a small molecule, NSC745885, derived from natural anthraquinone emodin, which down-regulated EZH2 via proteasome-mediated degradation. NSC745885 showed potent selective toxicity against multiple cancer cell lines but not normal cells. NSC745885 treatment overcame multiple-drug resistance and inhibited growth of resistant cancer cells. Over-expression of EZH2 in cancer cells attenuated effects of NSC745885, suggesting that down-regulation of EZH2 was responsible for growth inhibition of NSC745885. NSC745885 also suppressed tumor growth and down-regulated EZH2 in vivo. These results indicate that NSC7455889 suppresses bladder cancer by targeting EZH2.

Temporal expression patterns of distinct cytokines and M1/M2 macrophage polarization regulate rheumatoid arthritis progression

Mol Biol Rep 2020 May;47(5):3423-3437.PMID:32277445DOI:10.1007/s11033-020-05422-6.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation of synovial joints and often associated with chronic pain. Chronic joint inflammation is attributed to severe proliferation of synoviocytes and resident macrophages and infiltration of immune cells. These cells secrete pro-inflammatory cytokines such as tumor necrosis factor α (TNF-α), interleukin 6 (IL-6) and IL-17 to overcome actions of anti-inflammatory cytokines, thereby maintaining chronic inflammation and pain. The imbalance between pro-inflammatory cytokines (produced by M1 macrophages) and anti-inflammatory cytokines (produced by M2 macrophages) is a feature of RA progression, but the switch time of M1/M2 polarization and which receptor regulates the switch remain unsolved. Here we used an established RA mouse model to demonstrate that TNF-α expression was responsible for the initial acute stage of inflammation and pain (1-4 weeks), IL-17 expression the transition stage (4-12 weeks), and IL-6 expression the later maintenance stage (> 12 weeks). The switch time of M1/M2 polarization occurred at 4-8 weeks. We also identified a potential compound, anthra[2,1-c][1,2,5] thiadiazole-6,11-dione (NSC745885), that specifically inhibited T-cell death-associated gene 8 (TDAG8) function and expression. NSC745885 decreased joint inflammation and destruction and attenuated pain by reducing cytokine production and regulating the M1/M2 polarization switch. TDAG8 may participate in regulating the M1/M2 polarization and temporal expression of distinct cytokines to control RA progression.

Novel Anthra[1,2-c][1,2,5]Thiadiazole-6,11-Diones as Promising Anticancer Lead Compounds: Biological Evaluation, Characterization & Molecular Targets Determination

PLoS One 2016 Apr 21;11(4):e0154278.PMID:27100886DOI:10.1371/journal.pone.0154278.

The novel compounds NSC745885 and NSC757963 developed at our laboratory were tested against a panel of 60 cancer cell lines at the National Cancer Institute, USA, and a panel of 39 cancer cell lines at the Japanese Foundation of Cancer Research. Both compounds demonstrated selective unique multi-log differential patterns of activity, with GI50 values in the sub-micro molar range against cancer cells rather than normal cardiac cells. NSC757963 showed high selectivity towards the leukemia subpanel. Activities of both compounds strongly correlated to expression of NFKB1 and CSNK2B genes, implying that they may inhibit the NF-κB pathway. Immunocytochemical microscopy of OVCAR-3 cells showed clear cytosolic accumulation of the NF-κB p65 subunit following treatment. Western blotting showed dose dependent inhibition of the nuclear expression of the NF-κB p65 subunit with subsequent accumulation in the cytosol following treatment. Docking experiments showed binding of both compounds to the NF-κB activator IKKβ subunit preventing its translocation to the nucleus. Collectively, these results confirm the ability of our compounds to inhibit the constitutively active NF-κB pathway of OVCAR-3 cells. Furthermore, COMPARE analysis indicated that the activity of NSC757963 is similar to the antituberculosis agent rifamycin SV, this was confirmed by testing the antimycobacterial activity of NSC757963 against Mycobacterium tuberculosis, results revealed potent activity suitable for use in clinical practice. Molecular properties and Lipinski's parameters predicted acceptable bioavailability properties with no indication of mutagenicity, tumorigenicity, irritability and reproductive effects. Oral absorption experiments using the human Caco-2 model showed high intestinal absorption of NSC745885 by passive transport mechanism with no intestinal efflux or active transport mechanisms. The unique molecular characterization as well as the illustrated anticancer spectra of activity and bioavailability properties warrant further development of our compounds and present a foundation brick in the pre-clinical investigations to implement such compounds in clinical practice.

Different roles of p53 in the regulation of DNA damage caused by 1,2-heteroannelated anthraquinones and doxorubicin

Int J Biochem Cell Biol 2011 Dec;43(12):1720-8.PMID:21856437DOI:10.1016/j.biocel.2011.08.006.

The anthracyclin antibiotic agent doxorubicin (DXR) has been widely used as a chemotherapeutic drug for more than 40 years, but its clinical use has been limited by its cardiotoxicity. The mechanism of action of DXR remains uncertain and controversial. A series of 1,2-heteroannelated anthraquinones and anthra[1,2-d]imidazole-6,11-dione compounds were synthesized and their cytotoxicity profiles were analyzed using the National Cancer Institute 60 (NCI 60) platform and human telomerase inhibition assays. In the current study, three of the 1,2-heteroannelated anthraquinones, NSC745795, NSC745885 and NSC745887, were found to differ from each other with respect to their effects on cell cycle regulation, apoptosis, autophagy, senescence and their abilities to induce DNA damage. The differences depended on the presence or absence of a heterocyclic moiety, which suggested that the differences were due, at least in part, to differential effects on specific cellular targets, such as p53. In contrast to DXR, which induced p53 expression, treatment with NSC745885 resulted in the degradation of several proteins, including p53, via proteasome-dependent and -independent pathways in HeLa cells. These results provide insights into the molecular mechanisms governing cell inhibition by 1,2-heteroannelated anthraquinone derivatives and suggest that these mechanisms could serve as the basis for new structure-based drug designs.