PF-543 (Sphingosine Kinase 1 Inhibitor II) 是一种有效，选择性，可逆和鞘氨醇竞争性SPHK1抑制剂，IC50为 2 nM，Ki为 3.6 nM。PF-543 对SPHK1的选择性是 SPHK2 的 100 倍以上。PF-543 还是有效的全血中 1-磷酸鞘氨醇 (S1P) 形成的有效抑制剂，IC50为 26.7 nM。PF-543 诱导细胞凋亡，坏死和自噬。
| 生物活性 | PF-543 (Sphingosine Kinase 1 Inhibitor II) is a potent, selective, reversible and sphingosine-competitiveSPHK1inhibitor with anIC50of 2 nM and aKiof 3.6 nM. PF-543 is >100-fold selectivity forSPHK1overSPHK2. PF-543 is an effective potent inhibitor ofsphingosine 1-phosphate (S1P)formation in whole blood with anIC50of 26.7 nM. PF-543 inducesapoptosis, necrosis, andautophagy[1][2][3]. |
| IC50& Target | IC50: 2 nM (SPHK1); 26.7 nM (Sphingosine 1-phosphate (S1P))[1]
Ki: 3.6 nM (SPHK1)[1] |
体外研究
(In Vitro) | PF-543 (10-1000 nM; 24 hours; PASM cells) treatment abolishes SK1 expression at nM concentrations[2].
PF-543 (0.1-10 μM; 24 hours; PASM cells) treatment induces caspase-3/7 activity[2].
PF-543 inhibits C17-S1P formation in 1483 cells with an IC50of 1.0 nM[1].
SphK1 inhibition by PF-543 causes a dose-dependent depletion of the intracellular level of S1P with EC50concentration of 8.4 nM and a concomitant elevation of the intracellular level of sphingosine in 1483 cells. The level of endogenous S1P in 1483 cells after a 1 h treatment with 200 nM PF-543 is decreased 10-fold, producing a proportional increase in the level of sphingosine[1].
Western Blot Analysis[2] | Cell Line: | Human pulmonary arterial smooth muscle (PASM) cells | | Concentration: | 10 nM, 100 nM, 1000 nM | | Incubation Time: | 24 hours | | Result: | Abolished SK1 expression at nM concentrations. |
Apoptosis Analysis[2] | Cell Line: | Human pulmonary arterial smooth muscle (PASM) cells | | Concentration: | 0.1 μM, 1 μM, 10 μM | | Incubation Time: | 24 hours | | Result: | Induced caspase-3/7 activity in cultured human pulmonary smooth muscle cells. |
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体内研究
(In Vivo) | PF-543 (1 mg/kg; intraperitoneal injection; every second day; for 21 days; female C57BL/6 J mice) treatment has no effect on vascular remodelling but reduces right ventricular hypertrophy. The protection involves a reduction in the expression of p53 and an increase in the expression of anti-oxidant nuclear factor Nrf-2[2].
Mice are initially dosed (ip) with 10 mg/kg or 30 mg/kg of PF-543 for 24 h and the T1/2is 1.2 h in blood samples. Administration of 10 mg/kg PF-543 for 24 h to mice induces a decrease in SK1 expression in pulmonary vessels[2].
| Animal Model: | Female C57BL/6 J mice (7-12 week-old) with hypoxic-induced pulmonary arterial hypertension[2] | | Dosage: | 1 mg/kg | | Administration: | Intraperitoneal injection; every second day; for 21 days | | Result: | Reduced right ventricular hypertrophy. The protection involves a reduction in the expression of p53 (that promotes cardiomyocyte death) and an increase in the expression of anti-oxidant nuclear factor Nrf-2. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | Please store the product under the recommended conditions in the Certificate of Analysis. |
| 溶解性数据 | In Vitro: DMSO : 100 mg/mL(214.78 mM;Need ultrasonic) 配制储备液 | 1 mM | 2.1478 mL | 10.7388 mL | 21.4777 mL | | 5 mM | 0.4296 mL | 2.1478 mL | 4.2955 mL | | 10 mM | 0.2148 mL | 1.0739 mL | 2.1478 mL |
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