Opaganib (ABC294640)

製品コードS7174 バッチS717403

化学情報

	Synonyms	N/A	Storage (From the date of receipt)	3 years -20°C powder 1 years -80°C in solvent
	化学式	C₂₃H₂₅ClN₂O
	分子量	380.91	CAS No.	915385-81-8
Solubility (25°C)*	体外	DMSO	76 mg/mL warmed with 50ºC water bath (199.52 mM)
		Ethanol	28 mg/mL (73.5 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	Opaganib (ABC294640) is an orally bioavailable and selective sphingosine kinase-2 (SphK2) inhibitor with IC50 of approximately 60 μM. Phase 1/2.
in vitro	ABC294640 markedly alters the ratio of ceramide/S1P consistent with inhibition of SK activity in MDA-MB-231 cells. ABC294640 inhibits tumor cell proliferation with IC50 values ranging from approximately 6 to 48 μM, and impairs tumor cell migration concomitant with loss of microfilaments. ^[1] ABC294640 induces nonapoptotic cell death, morphological changes in lysosomes, formation of autophagosomes, and increases in acidic vesicles in A-498, PC-3, and MDA-MB-231 cells. ^[2] In both MCF-7 and ER-transfected HEK293 cells, ABC294640 decreases E2-stimulated ERE-luciferase activity. ^[3]
in vivo	In mice bearing mammary adenocarcinoma xenografts, ABC294640 (100 mg/kg, p.o.) significantly reduce tumor growth, associated with depletion of S1P levels. ^[1] In severe combined immunodeficient mice bearing A-498 xenografts, ABC294640 delays tumor growth and elevates autophagy markers. ^[2] ABC294640 protects against liver transplantation-induced inflammation and cross-talk between innate and adaptive immunities, major events precipitating and exacerbating graft injury, and improves liver function and survival. ^[4]

プロトコル(参考用のみ)

キナーゼアッセイ	Sphingosine Kinase Assays
キナーゼアッセイ	The IC50 values for ABC294640 and DMS are determined by a newly developed HPLC-based SK activity assay. In brief, the test compounds are incubated with recombinant SK1 or SK2 and NBD-Sph in the isozyme-selective assay buffers detailed below with 1 mg/ml fatty acid-free bovine serum albumin, 100 μM ATP, and 400 μM MgCl₂. The product, i.e., NBD-S1P, is separated from NBD-Sph by HPLC as follows: Waters 2795 HPLC system with a Waters 2495 fluorescence detector, C8 Chromolith RP-8e column (100 × 4.6 mm), 1 ml/min mobile phase (acetonitrile/20 mM sodium phosphate buffer, pH2.5, at 45:55). Fluorescence is monitored with excitation at 465 nm and emission at 531 nm. The ratio of NBD-S1P/(NBD-Sph + NBD-S1P) is used as a measure of SK activity. SK-isozyme selective assay buffers each contained 20 mM Tris, pH7.4, 5 mM EDTA, 5 mM EGTA, 3 mM β-mercaptoethanol, 5% glycerol, 1× protease inhibitors and 1× phosphatase inhibitors. For the SK1 assay buffer, 0.25% (final) Triton X-100 is added; and for the SK2 buffer, 1 M (final) KCl is added. Assays are run for 2 h at room temperature, and then a 1.5 volume of methanol is added to terminate the kinase reaction. After 10 min, the samples are centrifuged at 20,000g to pellet the precipitated protein, and the supernatants are analyzed by HPLC. In experiments to determine the Ki for inhibition of SK2 by ABC294640, the ADP Quest assay system is used to measure kinase activity in the presence of varying concentrations of sphingosine and ABC294640. To determine the effects of ABC294640 on cellular SK activity, near-confluent MDA-MB-231 cells are serum-starved overnight, and then treated with varying concentrations of ABC294640. The cells are then incubated with [³H]sphingosine at a final concentration of 1 μM. The cells take up the exogenous sphingosine, which is converted to S1P via SK activity, and [³H]S1P is separated from [³H]sphingosine by extraction and quantified by scintillation counting.
細胞アッセイ	細胞株	1025LU, Hep-G2, A-498, MCF-7, Caco-2, MDA-MB-231, HT-29, Panc-1, DU145, T24, and SK-OV-3 cell lines
	濃度	~50 μM
	反応時間	72 h
	実験の流れ	To determine the effects of the test compounds on proliferation, cells are plated into 96-well microtiter plates and allowed to attach for 24 h. Varying concentrations of ABC294640 are added to individual wells and the cells are incubated for an additional 72 h. At the end of this period, the number of viable cells is determined by use of the sulforhodamine-binding assay. The percentage of cells killed is calculated as the percentage decrease in sulforhodamine-binding compared with control cultures. Regression analyses of inhibition curves are performed by use of GraphPad Prism.
動物実験	動物モデル	Female BALB/c mice bearing JC tumors
	投薬量	~100 mg/kg
	投与方法	p.o.

参考

[4] Liu Q, et al. PLoS One. 2012, 7(7), e41834.

+ 展开

カスタマーフィードバック

: Data from [Data independently produced by , , Inflammation, 2018, 41(4):1498-1507]

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：

Comprehensive metabolomics expands precision medicine for triple-negative breast cancer [ Cell Res, 2022, 10.1038/s41422-022-00614-0]	PubMed: 35105939
Injectable cartilage matrix hydrogel loaded with cartilage endplate stem cells engineered to release exosomes for non-invasive treatment of intervertebral disc degeneration [ Bioact Mater, 2022, 15:29-43]	PubMed: 35386360
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
Targeting sphingosine kinase 1/2 by a novel dual inhibitor SKI-349 suppresses non-small cell lung cancer cell growth [ Cell Death Dis, 2022, 13(7):602]	PubMed: 35831279
Upregulated flotillins and sphingosine kinase 2 derail AXL vesicular traffic to promote epithelial-mesenchymal transition [ J Cell Sci, 2022, 135(7)jcs259178]	PubMed: 35394045
Overcoming enzalutamide resistance in metastatic prostate cancer by targeting sphingosine kinase [ EBioMedicine, 2021, 72:103625]	PubMed: 34656931
SPHK Inhibitors and Zoledronic Acid Suppress Osteoclastogenesis and Wear Particle-Induced Osteolysis [ Front Pharmacol, 2021, 12:794429]	PubMed: 35237148
SphK2/S1P Promotes Metastasis of Triple-Negative Breast Cancer Through the PAK1/LIMK1/Cofilin1 Signaling Pathway [ Front Mol Biosci, 2021, 8:598218]	PubMed: 33968977
Sphingosine Kinase Inhibition Enhances Dimerization of Calreticulin at the Cell Surface in Mitoxantrone-Induced Immunogenic Cell Death [ J Pharmacol Exp Ther, 2021, 378(3):300-310]	PubMed: 34158403

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。

各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。