Skp2 Inhibitor C1
(Synonyms: SKPin C1) 目录号 : GC37648
An inhibitor of Skp2-mediated p27 degradation
Cas No.:432001-69-9
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
SKPin C1 is an inhibitor of Skp1-Cullin1-F-box (SCF) family protein Skp2-mediated p27 degradation.1 It binds to Skp2 at the Cdc kinase subunit 1 (Cks1) interaction interface and blocks ubiquitylation of p27 in a Cks1-dependent manner in vitro when used at a concentration of 50 μM. SKPin C1 increases nuclear accumulation of p27 in ECC-1 endometrial carcinoma cells.2
1.Wu, L., Grigoryan, A.V., Li, Y., et al.Specific small molecule inhibitors of Skp2-mediated p27 degradationChem. Biol.19(12)1515-1524(2012) 2.Pavlides, S.C., Huang, K.-T., Reid, D.A., et al.Inhibitors of SCF-Skp2/Cks1 E3 ligase block estrogen-induced growth stimulation and degradation of nuclear p27kip1: Therapeutic potential for endometrial cancerEndocrinology154(11)4030-4045(2013)
| Cas No. | 432001-69-9 | SDF | |
| 别名 | SKPin C1 | ||
| Canonical SMILES | S=C(S/1)N(CC2=CN=CC=C2)C(C1=C\C(C=C(Br)C=C3)=C3OCC(O)=O)=O | ||
| 分子式 | C18H13BrN2O4S2 | 分子量 | 465.34 |
| 溶解度 | DMSO: 25 mg/mL (53.72 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 | 2.149 mL | 10.7448 mL | 21.4897 mL |
| 5 mM | 0.4298 mL | 2.149 mL | 4.2979 mL |
| 10 mM | 0.2149 mL | 1.0745 mL | 2.149 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。
SKP2 targeted inhibition suppresses human uveal melanoma progression by blocking ubiquitylation of p27
Onco Targets Ther 2019 May 30;12:4297-4308.PMID:31213847DOI:10.2147/OTT.S203888.
Background: SKP2 is considered an oncogene involved in various malignancies. SKP2 protein is a critical subunit of the SKP1-CUL1-F-box (SCF) E3 ligase complex which affects the cell cycle profoundly by specifically recognizing cell cycle regulators and mediating their ubiquitylation and proteasomal degradation. SKP2 dysfunction is characteristic of many tumor cells. However, its role in uveal melanoma (UM) has not been elucidated. Materials and methods: We analyzed the expressions of SKP2 in different UM cell lines compared with normal pigment cell by RNA-seq, RT-qPCR and Western blot. We then knocked down SKP2 in OM431 and MUM2B cells and confirmed its roles in cell proliferation via CCK8 assay. The sensitivity of cells to Skp2 Inhibitor C1 (SKPin C1) in vitro was evaluated by CCK8 assay and colony formation assay, and the sensitivity of MUM2B cells to SKPin C1 in vivo was estimated using the nude mouse-based xenograft model. Western blot and Immunoprecipitation assay were performed to detect the change of p27 and its ubiquitylation level in UM cells treated with SKPin C1, respectively. Results: The results showed that SKP2 was significantly highly expressed in UM cells. SKP2 promoted the progression of UM and knockdown of SKP2 inhibited cell proliferation in UM cells. Skp2 Inhibitor C1 that targets SKP2 essentially inhibits the growth of UM cells both in vivo and in vitro. Skp2 Inhibitor C1 decreased the degradation of p27 by blocking ubiquitylation of p27, resulting in p27 accumulation and cell cycle arrest in UM cells. Conclusion: Our findings demonstrated that SKP2 targeted inhibition suppresses UM cell proliferation and provides new options and possibilities for targeted therapies in UM.
Targeted pharmacologic inhibition of S-phase kinase-associated protein 2 (SKP2) mediated cell cycle regulation in lung and other RB-Related cancers: A brief review of current status and future prospects
Adv Biol Regul 2023 Mar 14;88:100964.PMID:37004354DOI:10.1016/j.jbior.2023.100964.
Small cell lung cancer (SCLC) often exhibits Rb deficiency, TRβ and p130 deletion, and SKP2 amplification, suggesting TRβ inactivation and SKP2 activation. It is reported that SKP2 targeted therapy is effective in some cancers in vitro and in vivo, but it is not reported for the treatment of SCLC and retinoblastoma. SKP2 is the synthetic lethal gene in SCLC and retinoblastoma, so SKP2 can be used for targeted therapy in SCLC and retinoblastoma. RB1 knockout mice develop several kinds of tumors, but Rb1 and SKP2 double knockout mice are healthy, suggesting that SKP2 targeted therapy may have significant effects on Rb deficient cancers with less side effects, and if successful in SCLC and retinoblastoma in vitro and in animal model, such compounds may be promising for the clinical treatment of SCLC, retinoblastoma, and variety of Rb deficient cancers. Previously our studies showed that retinoblastomas exhibit retinal cone precursor properties and depend on cone-specific thyroid hormone receptor β2 (TRβ2) and SKP2 signaling. In this study, we sought to suppress SCLC and retinoblastoma cell growth by SKP2 inhibitors as a prelude to targeted therapy in vitro and in vivo. We knocked down TRβ2 and SKP2 or over-expressed p27 in SCLC and retinoblastoma cell lines to investigate SKP2 and p27 signaling alterations. The SCLC cell lines H209 as well as retinoblastoma cell lines Y79, WERI, and RB177 were treated with Skp2 Inhibitor C1 at different concentrations, following which Western blotting, Immunostaining, and cell cycle kinetics studies were performed to study SKP2 and p27 expression ubiquitination, to determine impact on cell cycle regulation and growth inhibition. TRβ2 knockdown in Y79, RB177 and H209 caused SKP2 downregulation and degradation, p27 up-regulation, and S phase arrest, whereas, SKP2 knockdown or p27 over-expression caused p27 accumulation and G1-S phase arrest. In the cell lines Y79, WERI, RB177, and H209 treatment with C1 caused SKP2 ubiquitination and degradation, p27 de-ubiquitination and accumulation, and cell growth arrest. Skp2 Inhibitor C1 significantly suppressed retinoblastoma as well as SCLC cell growth by SKP2 degradation and p27 accumulation. In vivo study also showed inhibition of tumor growth with C1 treatment. Potential limitations of the success of such a therapeutic approach and its translational application in human primary tumors, and alternative approaches to overcome such limitations are briefly discussed for the treatment of retinoblastoma, SCLC and other RB-related cancers.
CD74 knockout attenuates alcohol intake-induced cardiac dysfunction through AMPK-Skp2-mediated regulation of autophagy
Biochim Biophys Acta Mol Basis Dis 2019 Sep 1;1865(9):2368-2378.PMID:31167126DOI:10.1016/j.bbadis.2019.05.020.
CD74, a non-polymorphic type II transmembrane glycoprotein and MHC class II chaperone, is the cell surface receptor for the inflammatory cytokine macrophage migration inhibitory factor (MIF) and participates in inflammatory signaling regulation. This study examined the potential role of CD74 in binge drinking-induced cardiac contractile dysfunction. WT and CD74 knockout mice were exposed to ethanol (3 g/kg/d, i.p., for 3 days). Echocardiography, cardiomyocyte function, histological staining and autophagy signaling including AMPK, mTOR, and AMPK downstream signals Skp2 and Sirt1 were evaluated. Our results revealed that ethanol challenge overtly compromised echocardiographic, cardiomyocyte contractile, intracellular Ca2+ and ultrastructural properties along with overt apoptosis, inflammation (elevated MIF, IL-1β and IL-6) and mitochondrial O2- production (p < 0.01), the effect of which was reconciled by CD74 ablation (p < 0.01 vs. ethanol group) with the exception of MIF expression. Ethanol challenge upregulated autophagy (p < 0.001), promoted AMPK phosphorylation and Sirt1 levels (p < 0.003) while suppressing mTOR phosphorylation and Skp2 levels (p < 0.02). These effects were reversed by CD74 ablation. In vitro studies demonstrated that short-term ethanol challenge compromised cardiomyocyte contractile function and facilitated GFP-Puncta formation, which were mitigated by CD74 knockout (p < 0.0001). Moreover, the CD74 ablation-offered beneficial effects against ethanol-induced cardiomyocyte dysfunction, and GFP-Puncta formation were nullified by the AMPK activator AICAR, the Skp2 Inhibitor C1 or the Sirt1 activator SRT1720 (p < 0.0001). Taken together, our data revealed that CD74 ablation counteracts acute ethanol challenge-induced myocardial dysfunction, inflammation and apoptosis possibly through an AMPK-mTOR-Skp2-mediated regulation of autophagy.