Sphingosine Kinase 1 Inhibitor II, PF-543 - CAS 1415562-82-1 - Calbiochem

别名

Sphingosine Kinase 1 Inhibitor II, PF-543 - CAS 1415562-82-1 - Calbiochem,SK Inhibitor II, ( R)-(1-(4-((3-Methyl-5-(phenylsulfonylmethyl)phenoxy)methyl)benzyl)-pyrrolidin-2-yl)methanol, Sphingosine Kinase Inhibitor II,SK Inhibitor II, (R)-(1-(4-((3-Methyl-5-(phenylsulfonylmethyl)phenoxy)methyl)benzyl)-pyrrolidin-2-yl)methanol, Sphingosine Kinase Inhibitor II

一般描述

A cell-permeable hydroxymethylpyrrolidine compound that acts as a high affinity (Kd = 5 nM, kofft1/2 = 8.5 min), but poor, sphingosine kinase-1/SphK1 substrate (1/1,500 of sphingosine processivity) and potently inhibits against SphK1-catalyzed sphingosine-to-S1P conversion (IC50 = 2.0 nM; [sphingosine] = 3 μM) in a reversible, sphingosine-, but not ATP-, competitive manner (Ki = 3.6 nM), exhibiting 132-fold selectivity over SphK2, no affinity toward S1P receptors (S1P1, S1P2, S1P3, S1P5), and much reduced or no inhibitory activity against a panel of 46 other lipid and protein kinases (IC50 >10 μM), including the structurally related diacylglyerol kinase α/DAGKα (3.7% inhibition at 10 μM). PF-543 exposure in 1483 squamous cultures is reported to result in intracellular S1P depletion (by 90% upon 1 h 200 nM or 7 d 1 μM drug exposure) with concomitant elevation of sphingosine level and no detectable cytotoxicity (1 μM for 7 to 9 d in 1483, A549, Jurkat, LN229, MCF7, or U937 cultures). Also active in human whole blood assays in the presence human & bovine serum proteins (IC50 = 26.7 nM against cellular C17-S1P formation from exogenously added 20 μM C17-sphingosine in 10 min with 30 min drug preincubation). A cell-permeable hydroxymethylpyrrolidine compound that inhibits sphingosine kinase-1/SphK1-catalyzed Sphingosine phosphorylation (IC50 = 2.0 nM; [sphingosine] = 3 μM) in a reversible and sphingosine-competitive manner (Ki = 3.6 nM), exhibiting no affinity toward S1P receptors and much reduced inhibitory activity against Sphk2 (6.8% inhibition at 10 μM) or 46 other lipid and portein kinases (IC50 >10 μM). Effectively depletes cellular S1P (by 90% with 1 h 200 nM or 7 d 1 μM drug exposure in 1483 cultures) with concomitant elevation of sphingosine level and no detectable cytotoxicity.

重悬

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.