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CAS No.: 1706522-79-3

PF-543 HCl/PF 543 盐酸盐 Catalog No. CSN23038

Synonyms: Sphingosine Kinase 1 Inhibitor II hydrochloride

PF-543 HCl is a cell-permeant inhibitor of SphK1 with a Ki of 3.6 nM, PF-543 is sphingosine-competitive and is more than 100-fold selective for SphK1 over the SphK2 isoform.

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技术信息

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 K_i value of 3.6nM^[1].
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

实验方案

计算器摩尔计算器总药量计算器工作液计算器
储存液制备
- 1 mg
- 5 mg
- 10 mg
- 1 mM
- 1.9918 mL
- 9.9588 mL
- 19.9175 mL
- 5 mM
- 0.3984 mL
- 1.9918 mL
- 3.9835 mL
- 10 mM
- 0.1992 mL
- 0.9959 mL
- 1.9918 mL

技术信息

CAS号

1706522-79-3

储存条件

粉末: Inert atmosphere,2-8°C

液体: -20°C:3-6 月 -80°C:12月

分子式

C27H32ClNO4S

运输

蓝冰

分子量

502.07

别名

Sphingosine Kinase 1 Inhibitor II hydrochloride

溶解度

DMSO	92.0 mg/mL (183.2 mM)
Water	Insoluble
Ethanol	92.0 mg/mL (183.2 mM)

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PF-543 HCl/PF 543 盐酸盐 Catalog No. CSN23038

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