SC 79
(Synonyms: 2-氨基-6-氯-ALPHA-氰基-3-(乙氧羰基)-4H-1-苯并吡喃-4-乙酸乙酯) 目录号 : GC11645
SC 79 是大脑中渗透性 Akt 磷酸化的激活剂和 AKT-PH 结构域易位的抑制剂。
Cas No.:305834-79-1
Sample solution is provided at 25 µL, 10mM.
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Related Biological Data
Activation of PFK1 and PFKFB3 is due to phosphorylation of AKT and AMPK. (F) Representative images of ARS and ALP staining in MC3T3-E1 cells after treatment with SC79 and PFK15.
MK-2206 dihydrochloride (GC16304) and SC79 (GC11645) were obtained from GLPBIO.
Clin Transl Med 13.9 (2023): e1369. PMID: 37649137 IF: 10.6002 -
Related Biological Data
SC79 partially rescued the inhibitory effect of proliferation and migration caused by the knockdown of HRL-SC. a, b Western blot analysis showed that SC79 increased expression of p-AKT.
The medium was replaced with the medium containing 5 μg/mL of SC79 (10 μM, GlpBio) in AKT activation experiments.
Stem Cell Res Ther 13.1 (2022): 1-16. PMID: 35765088 IF: 7.4996 -
Related Biological Data
Melatonin inhibits the AKT/mTOR signaling to reduce autophagy and the expression of fibrotic proteins in HSFs. (E) Treatment with SC79 to activate the AKT/mTOR signaling rescued the melatonin-decreased AKT/mTOR signaling and fibrotic protein expression in HSFs.
HSFs were treated with vehicle (DMSO) or 200 μM melatonin and/or 10 μM SC79 (Glpbio) for 24 h.
Bba-Mol Basis Dis (2023): 166887. PMID: 37739092 IF: 6.2001 -
Related Biological Data
CST1 enhances SERPINB2 expression via AKT signaling pathway in bronchial epithelial cells. (C) SC-79 has a positive effect on SERPINB2 expression (n = 2).
BEAS-2B cells were stimulated with or without cytokines IL-4, IL-13, and IL-17A,17 stimulated with or without house dust mite, treated with or without E64d, induced with SC-79 (4 μg/mL, AKT activator; GlpBio) or MK2206USA).
Allergy Asthma Immun 15.3 (2023): 374. PMID: 37075800 IF: 4.4 -
Related Biological Data
Rescue experiments were conducted to verify the mechanism of TOP2A regulating OC cell behavior. (a-c) after SC79 treatment of cells in the SH-TOP2A group, WB results suggested that the levels of p-AKT/AKT and p-mTOR/mTOR were increased.
Lyophilized SC79 (GC11645, Glpbio), an activator of AKT, was resuspended in 500 μL of DMSO at 20 μg/μL, followed by storage at −20°C for later use.
Cancer Biol Ther 25.1 (2024): 2325126. PMID: 38445610 IF: 3.5999
Quality Control & SDS
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- Purity: >98.00%
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- SDS (Safety Data Sheet)
- Datasheet
| Kinase experiment [1]: | |
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Preparation Method |
Hela cells were serum-starved for 1 h, treated with IGF or SC 79 (4 μg/mL) for 30 min, lysed in lysis buffer, supplemented with protease inhibitors, and analyzed for phospho-Akt by Western blotting |
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Reaction Conditions |
SC 79 (4 μg/mL) for 30 min |
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Applications |
SC 79, which inhibits PH AkT-GFP plasma membrane translocation but enhances Akt phosphorylation and activation in the cytosols |
| Cell experiment [1]: | |
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Cell lines |
HsSultan and NB4 cells |
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Preparation Method |
SC 79(8 ug/mL) was added to HsSultan or NB4 cell medium and incubated overnight (16-20 h). |
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Reaction Conditions |
8 ug/mL SC 79 for 16-20 h |
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Applications |
SC 79 enhances phosphorylation of all three Akt isotypes and enhances Akt activation in a variety of cell types. |
| Animal experiment [1]: | |
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Animal models |
MCAO mice |
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Preparation Method |
SC 79 was administered by intraperitoneal injection at a concentration of 0.04mg/g body weight. |
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Dosage form |
0.04mg/g SC 79 |
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Applications |
SC 79 enhances Akt activity during neuronal cell death in an in vivo mouse model of ischemia, SC 79 attenuates stroke-induced neuron death. |
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References: [1]. Jo H, Mondal S, et,al. Small molecule-induced cytosolic activation of protein kinase Akt rescues ischemia-elicited neuronal death. Proc Natl Acad Sci U S A. 2012 Jun 26;109(26):10581-6. doi: 10.1073/pnas.1202810109. Epub 2012 Jun 11. PMID: 22689977; PMCID: PMC3387065. |
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SC 79 is an activator of osmotic Akt phosphorylation in the brain and an inhibitor of AKT-PH domain translocation[1].
SC 79 enhances phosphorylation of all three Akt isotypes and enhances Akt activation in a variety of cell types[1]. Treatment of BRAT1 knockdown cells with Akt activator SC 79 can improve their proliferation and reduces mitochondrial ROS concentration[4]. In both SH-SY5Y cells and primary murine dopaminergic neurons, pre-treatment with SC 79 largely inhibited hydrogen peroxide (H2O2)-induced cell viability reduction, apoptosis and necrosis. SC 79 activated Akt in the neuronal cells, which was required for its neuroprotection against H2O2[5]. In primary murine osteoblasts and osteoblastic MC3T3-E1 cells, pretreatment with SC 79 significantly attenuated Dex-induced cell death. Further, Dex-induced mitochondrial permeability transition pore (mPTP) opening, cytochrome C release and apoptosis activation were dramatically alleviated with SC 79 pretreatment in above cells[6]. The protective role of SC 79 against H/R of hepatocytes or hepatic I/R injury is related to activation of phosphorylation of Akt, resulting in the decrease of pro-apoptotic protein of Bim, Bax, and Bad, and increase of the anti-apoptotic protein Bcl-2 and Bcl-xL induced by cell H/R and hepatic I/R injury[7].
SC 79 enhances Akt activity during neuronal cell death in an in vivo mouse model of ischemia, SC 79 attenuates stroke-induced neuron death[1]. SC 79 protects hepatocytes from apoptosis induced by agonistic anti-Fas antibody CH11 (for humans) or Jo2 (for mice) and significantly prolongs the survival of mice given a lethal dose of Jo2[2]. Akt activator SC 79 protects hepatocytes from TNF-α-induced apoptosis and protects mice from d-galactosamine (d-Gal)/lipopolysaccharide (LPS)-induced TNF-α-mediated liver injury and damage. SC 79 not only enhances the nuclear factor-κB (NF-κB) prosurvival signaling in response to TNF-α stimulation, but also increases the expression of cellular FLICE (FADD-like IL-1β-converting enzyme)-inhibitory protein L and S (FLIPL/S), which consequently inhibits the activation of procaspase-8[2].
References:
[1]: Jo H, Mondal S, et,al. Small molecule-induced cytosolic activation of protein kinase Akt rescues ischemia-elicited neuronal death. Proc Natl Acad Sci U S A. 2012 Jun 26;109(26):10581-6. doi: 10.1073/pnas.1202810109. Epub 2012 Jun 11. PMID: 22689977; PMCID: PMC3387065.
[2]: Liu W, Jing ZT, et,al. A Novel AKT Activator, SC79, Prevents Acute Hepatic Failure Induced by Fas-Mediated Apoptosis of Hepatocytes. Am J Pathol. 2018 May;188(5):1171-1182. doi: 10.1016/j.ajpath.2018.01.013. PMID: 29673487.
[3]: Jing ZT, Liu W, et,al. AKT activator SC79 protects hepatocytes from TNF-α-mediated apoptosis and alleviates d-Gal/LPS-induced liver injury. Am J Physiol Gastrointest Liver Physiol. 2019 Mar 1;316(3):G387-G396. doi: 10.1152/ajpgi.00350.2018. Epub 2019 Jan 10. PMID: 30629471.
[4]: So EY, Ouchi T. BRAT1 deficiency causes increased glucose metabolism and mitochondrial malfunction. BMC Cancer. 2014 Jul 29;14:548. doi: 10.1186/1471-2407-14-548. PMID: 25070371; PMCID: PMC4129107.
[5]: Xu Y, Gao YW, et,al. SC79 protects dopaminergic neurons from oxidative stress. Oncotarget. 2017 Dec 20;9(16):12639-12648. doi: 10.18632/oncotarget.23538. PMID: 29560097; PMCID: PMC5849161.
[6]: Li ST, Chen NN, et,al. SC79 rescues osteoblasts from dexamethasone though activating Akt-Nrf2 signaling. Biochem Biophys Res Commun. 2016 Oct 7;479(1):54-60. doi: 10.1016/j.bbrc.2016.09.027. Epub 2016 Sep 7. PMID: 27614310.
[7]: Zhou H, Yu Y,et,al. Protective Effects the Akt Activator SC79 in Hepatic Ischemia-Reperfusion Injury. Med Sci Monit. 2018 Jun 24;24:4346-4354. doi: 10.12659/MSM.911178. PMID: 29936516; PMCID: PMC6049012.
SC 79 是大脑中渗透性 Akt 磷酸化的激活剂和 AKT-PH 结构域易位的抑制剂[1]。
SC 79 增强所有三种 Akt 的磷酸化同种型并增强多种细胞类型中的 Akt 活化[1]。用 Akt 激活剂 SC 79 处理 BRAT1 敲低细胞可以改善它们的增殖并降低线粒体 ROS 浓度 [4]。在 SH-SY5Y 细胞和原代小鼠多巴胺能神经元中，用 SC 79 预处理在很大程度上抑制了过氧化氢 (H2O2) 诱导的细胞活力降低、细胞凋亡和坏死。 SC 79 激活神经元细胞中的 Akt，这是其针对 H2O2 的神经保护作用所必需的 [5]。在原代小鼠成骨细胞和成骨细胞 MC3T3-E1 细胞中，用 SC 79 预处理显着减弱了 Dex 诱导的细胞死亡。此外，SC 79 预处理上述细胞后，Dex 诱导的线粒体通透性转换孔 (mPTP) 打开、细胞色素 C 释放和细胞凋亡激活得到显着缓解 [6]。 SC 79 对肝细胞 H/R 或肝 I/R 损伤的保护作用与激活 Akt 磷酸化有关，导致 Bim、Bax 和 Bad 促凋亡蛋白减少，抗细胞 H/R 和肝 I/R 损伤诱导的凋亡蛋白 Bcl-2 和 Bcl-xL[7]。
SC 79 在体内小鼠缺血模型中增强神经元细胞死亡期间的 Akt 活性， SC 79 可减轻中风引起的神经元死亡[1]。 SC 79 可保护肝细胞免受激动性抗 Fas 抗体 CH11（用于人类）或 Jo2（用于小鼠）诱导的细胞凋亡，并在给予致死剂量的 Jo2[2] 后显着延长小鼠的存活期。 Akt 激活剂 SC 79 保护肝细胞免受 TNF-α 诱导的细胞凋亡，并保护小鼠免受 d-半乳糖胺 (d-Gal)/脂多糖 (LPS) 诱导的 TNF-α 介导的肝损伤和损伤。 SC 79 不仅增强核因子-κ；B (NF-κ；B) 响应 TNF-α 的促存活信号；刺激，但也会增加细胞 FLICE（FADD 样 IL-1β；-转化酶）-抑制蛋白 L 和 S (FLIPL/S) 的表达，从而抑制 procaspase-8 的激活[2].
| Cas No. | 305834-79-1 | SDF | |
| 别名 | 2-氨基-6-氯-ALPHA-氰基-3-(乙氧羰基)-4H-1-苯并吡喃-4-乙酸乙酯 | ||
| 化学名 | ethyl 2-amino-6-chloro-4-(1-cyano-2-ethoxy-2-oxoethyl)-4H-chromene-3-carboxylate | ||
| Canonical SMILES | CCOC(C(C(C(C(OCC)=O)=C1N)C2=C(O1)C=CC(Cl)=C2)C#N)=O | ||
| 分子式 | C17H17ClN2O5 | 分子量 | 364.78 |
| 溶解度 | ≥ 36.5mg/mL in DMSO | 储存条件 | Store at -20°C,unstable in solution, ready to use. |
| 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 | 2.7414 mL | 13.7069 mL | 27.4138 mL |
| 5 mM | 0.5483 mL | 2.7414 mL | 5.4828 mL |
| 10 mM | 0.2741 mL | 1.3707 mL | 2.7414 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。
Clinicopathologic features of kinase fusion-related thyroid carcinomas: an integrative analysis with molecular characterization
Mod Pathol2020 Dec;33(12):2458-2472.PMID: 32737449DOI: 10.1038/s41379-020-0638-5
The discovery of actionable kinase gene rearrangements has revolutionized the therapeutic landscape of thyroid carcinomas. Unsolved challenges include histopathologic recognition of targetable cases, correlation between genotypes and tumor behavior, and evolving resistance mechanisms against kinase inhibitors (KI). We present 62 kinase fusion-positive thyroid carcinomas (KFTC), including 57 papillary thyroid carcinomas (PTC), two poorly differentiated thyroid carcinomas (PDTC), two undifferentiated thyroid carcinomas (ATC), and one primary secretory carcinoma (SC), in 57 adults and 5 adolescents. Clinical records, post-operative histology, and molecular profiles were reviewed. Histologically, all KFTC showed multinodular growth with prominent intratumoral fibrosis. Lymphovascular invasion (95%), extrathyroidal extension, gross and microscopic (63%), and cervical lymph node metastasis (79%) were common. Several kinase fusions were identified: STRN-ALK, EML4-ALK, AGK-BRAF, CUL1-BRAF, MKRN1-BRAF, SND1-BRAF, TTYH3-BRAF, EML4-MET, TFG-MET, IRF2BP2-NTRK1, PPL-NTRK1, SQSTM1-NTRK1, TPR-NTRK1, TPM3-NTRK1, EML4-NTRK3, ETV6-NTRK3, RBPMS-NTRK3, SQSTM1-NTRK3, CCDC6-RET, ERC1-RET, NCOA4-RET, RASAL2-RET, TRIM24-RET, TRIM27-RET, and CCDC30-ROS1. Individual cases also showed copy number variants of EGFR and nucleotide variants and indels in pTERT, TP53, PIK3R1, AKT2, TSC2, FBXW7, JAK2, MEN1, VHL, IDH1, PTCH1, GNA11, GNAQ, SMARCA4, and CDH1. In addition to thyroidectomy and radioactive iodine, ten patients received multi-kinase and/or selective kinase inhibitor therapy, with 6 durable, objective responses and four with progressive disease. Among 47 cases with >6 months of follow-up (median [range]: 41 [6-480] months), persistent/recurrent disease, distant metastasis and thyroid cancer-related death occurred in 57%, 38% and 6%, respectively. In summary, KFTC encompass a spectrum of molecularly diverse tumors with overlapping clinicopathologic features and a tendency for clinical aggressiveness. Characteristic histology with multinodular growth and prominent fibrosis, particularly when there is extensive lymphovascular spread, should trigger molecular testing for gene rearrangements, either in a step-wise manner by prevalence or using a combined panel. Further, our findings provide information on molecular therapy in radioiodine-refractory thyroid carcinomas.
Novel Akt activator SC-79 is a potential treatment for alcohol-induced osteonecrosis of the femoral head
Oncotarget2017 May 9;8(19):31065-31078.PMID: 28415692DOI: 10.18632/oncotarget.16075
Alcohol is a leading risk factor for osteonecrosis of the femoral head (ONFH). We explored the molecular mechanisms underlying alcohol-induced ONFH and investigated the protective effect of the novel Akt activator SC-79 against this disease. We found that ethanol inhibited expression of the osteogenic genes RUNX2 and OCN, downregulated osteogenic differentiation, impaired the recruitment of Akt to the plasma membrane, and suppressed Akt phosphorylation at Ser473, thereby inhibiting the Akt/GSK3¦¯¦catenin signaling pathway in bone mesenchymal stem cells. To assess SC-79's ability to counteract the inhibitory effect of ethanol on Akt-Ser73 phosphorylation, we performed micro-computerized tomography and immunofluorescent staining of osteopontin, osteocalcin and collagen type 1 in a rat model of alcohol-induced ONFH. We found that SC-79 injections inhibited alcohol-induced osteonecrosis. These results show that alcohol-induced ONFH is associated with suppression of p-Akt-Ser473 in the Akt/GSK3¦¯¦catenin signaling pathway in bone mesenchymal stem cells. We propose that SC-79 treatment to rescue Akt activation could be tested in the clinic as a potential therapeutic approach to preventing the development of alcohol-induced ONFH.
Improved Sc-44 production in a siphon-style liquid target on a medical cyclotron
Appl Radiat Isot2021 Jun;172:109675.PMID: 33756396DOI: 10.1016/j.apradiso.2021.109675
In order to use new and promising radiometals for molecular imaging, it is important that they can be obtained as inexpensively and easily as possible. This often requires a cyclotron with solid target hardware or a radionuclide generator, which are not widely available for rarely used radionuclides. Here, we investigate the improved production of 44Sc with a siphon-style liquid target system and compare to our previous work with a simple liquid target. A metal salt solution with a high concentration of natural abundance Ca(NO3)2 (0.14 g/cm3) was irradiated with a medical cyclotron (12 MeV protons; 20 ¦́). 44Sc was produced via the natCa(p,x)44Sc reaction. As the pressure increase during irradiation was reduced in the siphon-style target, it was possible to irradiate with a higher proton beam current (20 ¦́) than with the simple liquid target system (7.9 ¦́). In addition, the saturation yield per ¦́ of 44Sc was increased by a factor of 3.18 ¡À 0.05 (6.2 ¡À 0.1 MBq/¦́ with the siphon target versus 1.94 ¡À 0.08 MBq/¦́ with the simple target). This results in an overall increase in 44Sc activity by a factor of 11.
Liver metastases
Recent Results Cancer Res2006;167:79-89.PMID: 17044298DOI: 10.1007/3-540-28137-1_6
[Adrenal tumors]
Chirurg2008 Nov;79(11):1087-94; quiz 1095-6.PMID: 18941729DOI: 10.1007/s00104-008-1638-z
Adrenal tumors can be primary or secondary entities. Primary tumors are able to secrete hormones which may cause significant effects clinically. Typical tumor-related adrenal diseases are Conn's syndrome (hyperaldosteronism), Cushing's syndrome (hypercortisolism), and pheochromocytoma (catacholamine excess). Primary adrenal tumors are rarely malignant, but adrenocortical neoplasias show a relation between tumor size and rate of malignancy. Diagnostic methods for adrenal tumors include hormone tests and imaging. The first choice of treatment is surgical removal, today preferably by minimally invasive approaches.