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K145 HCl

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Chemical Structure| 1449240-68-9 同义名 : K145 (hydrochloride);K145 hydrochloride
CAS号 : 1449240-68-9
货号 : A295989
分子式 : C18H25ClN2O3S
纯度 : 99%+
分子量 : 384.921
MDL号 : MFCD28160629
存储条件：

粉末 Inert atmosphere,Store in freezer, under -20°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 50 mg/mL(129.9 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO

H2O: 120 mg/mL(311.75 mM)
动物实验配方：
生物活性
描述 Sphingosine kinases (SphKs) catalyze the conversion of the sphingosine to the promitogenic/migratory product, sphingosine-1-phosphate (S1P). SphK/S1P pathway has been linked to the progression of cancer and various other diseases including allergic inflammatory disease, cardiovascular diseases, rejection after transplantation, the central nervous system, and virus infections[1]. Gene-targeted mice null for the sphingosine kinase 1 isoform whose hearts are subjected to ischemia/reperfusion injury exhibit increased infarct size and respond poorly either to ischemic preconditioning or to ischemic postconditioning[2]. SphK2 is a nuclear protein that suppresses cell proliferation by inhibiting DNA synthesis, while also enhancing apoptosis in diverse cell types. Genetic inhibition of SphK2 did not significantly impact the severity or progression of inflammatory arthritis, while pharmacologic inhibition of SphK2 led to significantly more severe arthritis[3]. SphK2 is involved in regulating interleukin (IL)-12/interferon gamma (IFN-γ) and histone deacetylase-1/2 (HDAC-1/2) signalling and, potentially, retinoid-related orphan receptor gamma t (ROR-γt) stability linked with T helper (Th) 17 cell polarisation[4]. K145 inhibited the activity of SphK2 in a dose-dependent manner with an IC50 of 4.30 uM. The Lineweaver-Burk analysis revealed a Ki of 6.4±0.7 uM for SphK2 and indicated that K145 is a substrate competitive inhibitor (with sphingosine). K145 accumulates in U937 cells, suppresses the S1P level, and inhibits SphK2. K145 also exhibited inhibitory effects on the growth of U937 cells as well as apoptotic effects in U937 cells, and that these effects may be through the inhibition of downstream ERK and Akt signaling pathways[5].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.60mL

0.52mL

0.26mL

12.99mL

2.60mL

1.30mL

25.98mL

5.20mL

2.60mL
参考文献

[1]Mengda Cao,et al. Sphingosine kinase inhibitors: A patent review. Int J Mol Med. 2018 May;41(5):2450-2460.

[2]Joel S Karliner. Sphingosine kinase and sphingosine 1-phosphate in cardioprotection. J Cardiovasc Pharmacol. 2009 Mar;53(3):189-97.

[3]Tao Xu,et al. Sphingosine kinase 2: a controversial role in arthritis. Rheumatol Int. 2014 Jul;34(7):1015-6.

[4]Nigel J Pyne,et al. Sphingosine Kinase 2 in Autoimmune/Inflammatory Disease and the Development of Sphingosine Kinase 2 Inhibitors. Trends Pharmacol Sci. 2017 Jul;38(7):581-591.

[5]Liu K, et al. Biological characterization of 3-(2-amino-ethyl)-5-[3-(4-butoxyl-phenyl)-propylidene]-thiazolidine-2,4-dione (K145) as a selective sphingosine kinase-2 inhibitor and anticancer agent. PLoS One. 2013;8(2):e56471.