SC-43
目录号 : GC61524
An SHP-1 activator
Cas No.:1400989-25-4
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
SC-43 is an activator of Src homology region 2 domain-containing phosphatase 1 (SHP-1).1 It activates SHP-1 phosphatase activity in a cell-free assay and inhibits IL-6-induced phosphorylation of STAT3 in PLC/PRF/5 hepatocellular carcinoma cells when used at a concentration of 10 ?M. SC-43 inhibits the proliferation of PLC/PRF/5 cells (IC50 = 0.5 ?M). It decreases disease severity and improves survival in a mouse model of carbon tetrachloride-induced liver fibrosis when administered at doses of 10 and 20 mg/kg.2
1.Chen, K.-F., Tai, W.-T., Hsu, C.-Y., et al.Blockade of STAT3 activation by sorafenib derivatives through enhancing SHP-1 phosphatase activityEur. J. Med. Chem.55220-227(2012) 2.Su, T.-H., Shiau, C.-W., Jao, P., et al.Src-homology protein tyrosine phosphatase-1 agonist, SC-43, reduces liver fibrosisSci. Rep.7(1)1728(2017)
| Cas No. | 1400989-25-4 | SDF | |
| Canonical SMILES | O=C(NC1=CC=CC(OC2=CC=C(C#N)C=C2)=C1)NC3=CC=C(Cl)C(C(F)(F)F)=C3 | ||
| 分子式 | C21H13ClF3N3O2 | 分子量 | 431.8 |
| 溶解度 | DMSO: 250 mg/mL (578.97 mM) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 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。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 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 |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Accelerator Production of Scandium Radioisotopes: SC-43, Sc-44, and Sc-47
Curr Radiopharm 2021;14(4):359-373.PMID:33438551DOI:10.2174/1874471014999210112205535.
Scandium radioisotopes are increasingly considered viable radiolabels for targeted molecular imaging (SC-43, Sc-44) and therapy (Sc-47). Significant technological advances have increased the quantity and quality of available radioscandium in the past decade, motivated in part by the chemical similarity of scandium to therapeutic radionuclides like Lu-177. The production and radiochemical isolation techniques applied to scandium radioisotopes are reviewed, focusing on charged particle and electron linac initiated reactions and using calcium and titanium as starting materials.
Two novel SHP-1 agonists, SC-43 and SC-78, are more potent than regorafenib in suppressing the in vitro stemness of human colorectal cancer cells
Cell Death Discov 2018 Aug 13;4:25.PMID:30109144DOI:10.1038/s41420-018-0084-z.
Signal transducer and activator of transcription 3 (STAT3) has been shown to play a critical role in the maintenance of cancer stem cells (CSCs). Hence, the inhibition of STAT3 signaling has been suggested to be a viable therapeutic approach for cancers. Moreover, the efficacy of combinations of chemotherapeutic drugs and napabucasin, a small-molecule STAT3 inhibitor, have been assessed in various clinical trials, including those involving patients with metastatic colorectal cancer (CRC). Two recently developed small-molecule STAT3 inhibitors, SC-43 and SC-78, which can stimulate SHP-1 to inactivate STAT3, were found to have anti-tumor activity. In this study, the inhibitory effects of SC-43, SC-78, and regorafenib (a reference drug) on cell viability, STAT3 phosphorylation, and various stemness properties [e.g., sphere-forming and soft agar colony-forming abilities, CD133+/CD44+ (stem cell-like) subpopulations, and the expression of several CSC markers] were examined for both HCT-116 and HT-29 human CRC cells. We found that SC-43 and SC-78 but not regorafenib inhibited constitutive and IL-6-induced STAT3 phosphorylation in HCT-116 and HT-29 cells, respectively. Moreover, SC-43 and SC-78 were more potent than regorafenib in suppressing the stemness properties (except stem cell-like subpopulations) of these cells. As expected, SHP-1 knockdown almost completely abolished the suppressive effects of SC-43 and SC-78 on the sphere formation in both cell lines. Furthermore, SC-43 and SC-78 showed synergistic inhibitory effects with oxaliplatin and/or irinotecan on sphere formation. Overall, our results suggest that SC-43 and SC-78 are potent STAT3 inhibitors that may potentially be used in combination therapy for CRC.
Src-homology protein tyrosine phosphatase-1 agonist, SC-43, reduces liver fibrosis
Sci Rep 2017 May 11;7(1):1728.PMID:28496142DOI:10.1038/s41598-017-01572-z.
This study aimed to investigate the role of src-homology protein tyrosine phosphatase-1 (SHP-1)-signal transducer and activator of transcription 3 (STAT3) pathway in liver fibrogenesis and the anti-fibrotic effect of SHP-1 agonist. The antifibrotic activity of SC-43, a sorafenib derivative with an enhanced SHP-1 activity, was evaluated in two fibrosis mouse models by carbon tetrachloride induction and bile duct ligation. Rat, human, and primary mouse hepatic stellate cells (HSCs) were used for mechanistic investigations. The results showed that SHP-1 protein primarily localized in fibrotic areas of human and mouse livers. SC-43 treatment reduced the activated HSCs and thus effectively prevented and regressed liver fibrosis in both fibrosis mouse models and improved mouse survival. In vitro studies revealed that SC-43 promoted HSC apoptosis, increased the SHP-1 activity and inhibited phospho-STAT3. The enhanced SHP-1 activity in HSCs significantly inhibited HSC proliferation, whereas SHP-1 inhibition rescued SC-43-induced HSC apoptosis. Furthermore, SC-43 interacted with the N-SH2 domain of SHP-1 to enhance the activity of SHP-1 as its antifibrotic mechanism. In conclusion, the SHP-1-STAT3 pathway is crucial in fibrogenesis. SC-43 significantly ameliorates liver fibrosis through SHP-1 upregulation. A SHP-1-targeted antifibrotic therapy may represent a druggable strategy for antifibrotic drug discovery.
Fifty Shades of Scandium: Comparative Study of PET Capabilities Using SC-43 and Sc-44 with Respect to Conventional Clinical Radionuclides
Diagnostics (Basel) 2021 Oct 3;11(10):1826.PMID:34679525DOI:10.3390/diagnostics11101826.
Scandium-44 has been proposed as a valuable radionuclide for Positron Emission Tomography (PET). Recently, scandium-43 was introduced as a more favorable option, as it does not emit high-energy γ-radiation; however, its currently employed production method results in a mixture of scandium-43 and scandium-44. The interest in new radionuclides for diagnostic nuclear medicine critically depends on the option for image-based quantification. We aimed to evaluate and compare the quantitative capabilities of scandium-43/scandium-44 in a commercial PET/CT device with respect to more conventional clinical radionuclides (fluorine-18 and gallium-68). With this purpose, we characterized and compared quantitative PET data from a mixture of scandium-43/scandium-44 (~68% scandium-43), scandium-44, fluorine-18 and gallium-68, respectively. A NEMA image-quality phantom was filled with the different radionuclides using clinical-relevant lesion-to-background activity concentration ratios; images were acquired in a Siemens Biograph Vision PET/CT. Quantitative accuracy with scandium-43/scandium-44 in the phantom's background was within 9%, which is in agreement with fluorine-18-based PET standards. Coefficient of variance (COV) was 6.32% and signal recovery in the lesions provided RCmax (recovery coefficient) values of 0.66, 0.90, 1.03, 1.04, 1.12 and 1.11 for lesions of 10-, 13-, 17-, 22-, 28- and 37-mm diameter, respectively. These results are in agreement with EARL reference values for fluorine-18 PET. The results in this work showed that accurate quantitative scandium-43/44 PET/CT is achievable in commercial devices. This may promote the future introduction of scandium-43/44-labelled radiopharmaceuticals into clinical use.
A combination of sorafenib and SC-43 is a synergistic SHP-1 agonist duo to advance hepatocellular carcinoma therapy
Cancer Lett 2016 Feb 28;371(2):205-13.PMID:26679051DOI:10.1016/j.canlet.2015.11.039.
Sorafenib is the first and currently the only standard treatment for advanced hepatocellular carcinoma (HCC). We previously developed a sorafenib derivative SC-43, which exhibits much more enhanced anti-HCC activity than sorafenib and also promotes apoptosis in sorafenib-resistant HCC cells. Herein, a novel "sorafenib plus" combination therapy was developed by coupling sorafenib treatment with SC-43. Both sorafenib and SC-43 are proven Src homology region 2 domain containing phosphatase 1 (SHP-1) agonists. The combined actions of sorafenib and SC-43 enhanced SHP-1 activity, which was associated with diminished STAT3-related signals and stronger expression of apoptotic genes above that of either drug alone, culminating in increased cell death. Decreased p-STAT3 signaling and tumor size, as well as increased SHP-1 activity were observed in mice receiving the combination therapy in a subcutaneous HCC model. More reduced orthotopic HCC tumor size and prolonged survival were also observed in mice in the combination treatment arm compared to mice in either of the monotherapy arms. These results in the preclinical setting pave the way for further clinical studies to treat unresectable HCC.