SKI II

製品コードS7176 バッチS717601

印刷

化学情報

Chemical Structure Synonyms SphK-I2 Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C15H11ClN2OS
分子量 302.78 CAS No. 312636-16-1
Solubility (25°C)* 体外 DMSO 61 mg/mL (201.46 mM)
Ethanol 61 mg/mL (201.46 mM)
Water Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 SKI II (SphK-I2) is a highly selective and non ATP-competitive sphingosine kinase (SphK) inhibitor with IC50 of 0.5 μM, while exhibiting no inhibitory action on other kinases including PI3K, PKCα and ERK2.
in vitro SKI II potently inhibits endogenous SK activities in the breast cancer cell line MDA-MB-231. SKI II demonstrates significantly antiproliferative effects in human cancer cell lines including T-24, MCF-7, MCF-7/VP, NCI/ADR with IC50 of 4.6 μM , 1.2 μM, 0.9 μM and 1.3 μM, respectively. SKI II also induces apoptosis of T24 cells consistent with the hypothesized consequence of reducing S1P levels. [1] As demonstrated previously in MDA-MB-231 cells, SKI II decreases S1P formation in JC cells in a concentration-dependent manner, with IC50 of 12 μM. [2] In addition, SKI-II can reverse drug resistance of SGC7901/DDP to cisplatin by down-regulating expression of P-gp and up-regulating apoptosis through down-regulation of SphK1. [3]
in vivo SKI II (50 mg/kg) after intraperitoneal or oral administration significantly decreases tumor growth a syngeneic Balb/c mouse solid tumor model that uses JC mammary adenocarcinoma cells relative to control groups with no overt toxicity or weight loss.[2] SKI-II (50 mg/kg ip) ameliorates antigen-induced bronchial smooth muscle hyperresponsiveness in mice by endogenously inhibiting generation of S1P. [4]

プロトコル(参考用のみ)

キナーゼアッセイ SK Assay
A medium-throughput assay suitable for screening for inhibitors of recombinant human SK has been established. Briefly, 5 μg of purified GST-SK fusion protein are combined with 12 nM sphingosine, which contains a 100-fold dilution of [3-3H]sphingosine (20 Ci/mmol), 1 mM ATP, 1 mM magnesium chloride, and 200 μL of assay buffer [20 mM Tris HCl (pH 7.4), 20% glycerol, 1 mM beta-mercaptoethanol, 1 mM EDTA, 20 mM zinc chloride, 1 mM sodium orthovanadate, 15 mM sodium fluoride, and 0.5 mM 4-deoxypyridoxine]. Assays are run for 30 min at 25°C with shaking and contains either 1% DMSO or 5 g/mL test compound, which corresponds to concentrations of 10–25 μM. The reactions are terminated with 50 μL of concentrated ammonium hydroxide, followed by extraction of the assay mixture with chloroform:methanol (2:1). The aqueous portion is transferred to scintillation vials and radioactivity is quantified as a measure of [3H]]S1P formation using a Beckman LS 3801 Scintillation Counter. The intra-assay coefficient of variation is ~10%, whereas interassay variation is ~20%.
細胞アッセイ 細胞株 T-24, MCF-7, MCF-7/VP, NCI/ADR cell lines
濃度 ~50 μM
反応時間 48 hours
実験の流れ T24, MCF-7, MCF-7/VP, and NCI/ADR cells are plated into 96-well tissue culture plates at ~15% confluency. After 24 hours, cells are treated with various concentrations of inhibitors. After an additional 48 hours, cell survival is assayed using the sulforhodamine B assay.
動物実験 動物モデル JC xenografts are established in mice
投薬量 ~100 mg/kg
投与方法 Intraperitoneal administration or oral administration

カスタマーフィードバック

Data from [Data independently produced by , , Cancer Cell Int, 2018, 18:202]

Data from [Data independently produced by , , Breast Cancer Res Treat, 2018, 172(1):33-43]

Data from [Data independently produced by , , Neurochemistry International, 2016, 94: 90-97.]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

The central role of Sphingosine kinase 1 in the development of neuroendocrine prostate cancer (NEPC): A new targeted therapy of NEPC [ Clin Transl Med, 2022, 12(2):e695] PubMed: 35184376
The sphingosine kinase inhibitor SKI-V suppresses cervical cancer cell growth [ Int J Biol Sci, 2022, 18(7):2994-3005] PubMed: 35541904
The anti-osteosarcoma cell activity by the sphingosine kinase 1 inhibitor SKI-V [ Cell Death Discov, 2022, 8(1):48] PubMed: 35115496
Proteomic-Based Approach Reveals the Involvement of Apolipoprotein A-I in Related Phenotypes of Autism Spectrum Disorder in the BTBR Mouse Model [ Int J Mol Sci, 2022, 23(23)15290] PubMed: 36499620
MAPK activity dynamics regulate non-cell autonomous effects of oncogene expression [ Elife, 2020, 9e60541] PubMed: 32940599
Follicle-stimulating hormone promotes the proliferation of epithelial ovarian cancer cells by activating sphingosine kinase [ Sci Rep, 2020, 10(1):13834] PubMed: 32796926
The Intra-nuclear SphK2-S1P Axis Facilitates M1-to-M2 Shift of Microglia via Suppressing HDAC1-Mediated KLF4 Deacetylation. [ Front Immunol, 2019, 10:1241] PubMed: 31214192
Acid ceramidase promotes drug resistance in acute myeloid leukemia through NF-κB-dependent P-glycoprotein upregulation. [ J Lipid Res, 2019, 60(6):1078-1086] PubMed: 30962310
TRIM14 promotes colorectal cancer cell migration and invasion through the SPHK1/STAT3 pathway [Jin Z Cancer Cell Int, 2018, 18:202] PubMed: 30555277
Influence of sphingosine-1-phosphate signaling on HCMV replication in human embryonal lung fibroblasts [Zilch A Med Microbiol Immunol, 2018, 207(3-4):227-242] PubMed: 29700602

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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