567741

Sphingosine Kinase 1 Inhibitor II, PF-543

The Sphingosine Kinase 1 Inhibitor II, PF-543 controls the biological activity of Sphingosine Kinase 1. This small molecule/inhibitor is primarily used for Cell Structure applications.

• 別名: Sphingosine Kinase 1 Inhibitor II, PF-543, 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
• 実験式（ヒル表記法）: C₂₇H₃₁NO₄S
• CAS番号: 1415562-82-1
• 分子量: 465.60
• Enzyme Commission number: 465.6
• MDL番号: MFCD23098794
• UNSPSCコード: 12352200
• NACRES: NA.77

特性

• 品質水準: 100
• アッセイ: ≥95% (HPLC)
• 形状: solid
• メーカー／製品名: Calbiochem^®
• 保管条件: OK to freeze; protect from light
• 色: off-white
• 溶解性: DMSO: 50 mg/mL
• 輸送温度: ambient
• 保管温度: 2-8°C
• SMILES記法: O=S(C1=CC=CC=C1)(CC2=CC(C)=CC(OCC3=CC=C(CN4[C@@H](CO)CCC4)C=C3)=C2)=O
• InChI: 1S/C27H31NO4S/c1-21-14-24(20-33(30,31)27-7-3-2-4-8-27)16-26(15-21)32-19-23-11-9-22(10-12-23)17-28-13-5-6-25(28)18-29/h2-4,7-12,14-16,25,29H,5-6,13,17-20H2,1H3/t25-/m1/s1
• InChI Key: NPUXORBZRBIOMQ-RUZDIDTESA-N

詳細

詳細

A cell-permeable hydroxymethylpyrrolidine compound that acts as a high affinity (K_d = 5 nM, k_offt_1/2 = 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 (K_i = 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 (K_i = 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.

包装

Packaged under inert gas

警告

Toxicity: Standard Handling (A)

再構成

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

その他情報

Schnute, M.E., et al. 2012. Biochem. J.444, 79.

法的情報

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

安全性情報

• 保管分類コード: 11 - Combustible Solids
• WGK: WGK 3
• 引火点(°F): Not applicable
• 引火点(℃): Not applicable