产品说明书

	同义名 :	Sphingosine Kinase 1 Inhibitor II hydrochloride;PF-543 (hydrochloride);PF-543 hydrochloride
	CAS号 :	1706522-79-3
	货号 :	A451925
	分子式 :	C27H32ClNO4S
	纯度 :	99%+
	分子量 :	502.065
	MDL号 :	MFCD28411614
	存储条件：	粉末 Inert atmosphere,2-8°C 液体 -20°C:3-6个月-80°C:12个月
	溶解度 :	-
	动物实验配方：

生物活性
描述	Sphingosine 1-phosphate (S1P) is an extracellular ligand that regulates endothelial cell function and angiogenesis, promotes survival and migration of cancer cells, and acts as a key regulator of immune cell trafficking. S1P is formed primarily by the action of sphingosine kinases (SphKs). PF 543 is a potent, cell-permeant inhibitor of SphK1 with an IC50 value of 2.0 ± 0.6nM in an in vitro enzyme assay and is able to inhibit the enzyme >95% at 20 nM. PF-543 was also able to inhibit C17-S1P formation in 1483 cells with an IC50 value of 1.0 ± 0.3nM. PF-543 showed 132-fold selectivity for SphK1 over SphK2 (IC50 = 356nM). The inhibition of SphK1 by PF-543 led to a concentration-dependent depletion of the intracellular level of S1P with an EC50 value of 8.4nM. The presence of 1μM PF-543 for 7 days in the culture medium resulted in a 10-fold decrease in S1P and a 2-fold increase in sphingosine levels in 1483 cells. PF543 also potently inhibited C17-S1P formation in human whole blood with an IC50 value of 26.7 nM[1]. PF-543 treatment (0.93mg/kg body weight per day) for 28 days significantly decreased erythrocyte Sphk1 activity and reduced erythrocyte and plasma S1P levels in SCD Tg mice[2].
作用机制	PF 543 structurally resembles sphingosine and potentially could act as SphK1 substrate. It inhibits S1P binding to human recombinant SphK1 with a Ki value of 3.6nM[1].

实验方案
	1mg	5mg	10mg
1 mM 5 mM 10 mM	1.99mL 0.40mL 0.20mL	9.96mL 1.99mL 1.00mL	19.92mL 3.98mL 1.99mL

参考文献

[1]Schnute ME, McReynolds MD, Kasten T, Yates M, Jerome G, Rains JW, Hall T, Chrencik J, Kraus M, Cronin CN, Saabye M, Highkin MK, Broadus R, Ogawa S, Cukyne K, Zawadzke LE, Peterkin V, Iyanar K, Scholten JA, Wendling J, Fujiwara H, Nemirovskiy O, Wittwer AJ, Nagiec MM. Modulation of cellular S1P levels with a novel, potent and specific inhibitor of sphingosine kinase-1. Biochem J. 2012 May 15;444(1):79-88. doi: 10.1042/BJ20111929 [2]Zhang Y, Berka V, Song A, Sun K, Wang W, Zhang W, Ning C, Li C, Zhang Q, Bogdanov M, Alexander DC, Milburn MV, Ahmed MH, Lin H, Idowu M, Zhang J, Kato GJ, Abdulmalik OY, Zhang W, Dowhan W, Kellems RE, Zhang P, Jin J, Safo M, Tsai AL, Juneja HS, Xia Y. Elevated sphingosine-1-phosphate promotes sickling and sickle cell disease progression. J Clin Invest. 2014 Jun;124(6):2750-61. doi: 10.1172/JCI74604