Acid Ceramidase Inhibitor IV, BOC-Calbiochem

半岛bd体育手机客户端 说明

一般描述

A cell-permeable, chemically and metabolically stable (t_1/2>5 h in aqueous buffers at pH 4.5 and 7.4;t_1/2>2 h in murine plasma at 37 °C) benzoxazolone carboxamide (BOC) compound that inhibits acid ceramidase (AC) activity in a potent (IC₅₀= 79 nM against HEK293 lysosomal lysate AC activity) and selective manner via covalent modification of the active site Cys143, exhibiting little or no potency toward a panel of 15 enzymes, including proteases, lipoxygenases, cyclooxygenases, sPLA₂, and monoacylglycerol lipase (67% inhibition of cathepsin D and ≤17.1% inhibition of the rest at 10 ?M). Culture treatment results in long-lasting (>6 h) suppression of cellular AC activity in murine macrophage-like Raw 264.7 and human colon adenocarcinoma SW403 cells (IC₅₀with 3 h treatment = 400 and 825 nM, respectively), as well as built-ups of cellular AC substrates Cer(d18:0/16:0) & Cer(d18:1/16:0) in a dose-dependent manner. Intraperitoneal injection (10 mg/kg) effectively inhibits tissue AC activity in multiple organs, including lung, heart, kidney, brain hippocampus, and liver (by 70%, 60%, 44%, 40%, 35%, respectively), with good pharmacokinetic properties (T_max= 30 min,C_max= 1.768 ?g/mL,t_1/2= 458 min, AUC_{0-8 h}= 0.31 mg·min/mL; 10 mg/kg i.p.).
A cell-permeable, chemically and metabolically stable (t_1/2>5 h in aqueous buffers at pH 4.5 and 7.4;t_1/2>2 h in murine plasma at 37 °C) benzoxazolone carboxamide (BOC) compound that inhibits acid ceramidase (AC) activity in a potent (IC₅₀= 79 nM against HEK293 lysosomal lysate AC activity) and selective manner via covalent modification of the active site Cys143, exhibiting little or no potency toward a panel of 15 enzymes, including proteases, lipoxygenases, cyclooxygenases, sPLA₂, and monoacylglycerol lipase (67% inhibition of cathepsin D and ≤17.1% inhibition of the rest at 10 ?M). Culture treatment results in long-lasting (>6 h) suppression of cellular AC activity in murine macrophage-like Raw 264.7 and human colon adenocarcinoma SW403 cells (IC₅₀with 3 h treatment = 400 and 825 nM, respectively), as well as built-ups of cellular AC substrates Cer(d18:0/16:0) & Cer(d18:1/16:0) in a dose-dependent manner. Intraperitoneal injection (10 mg/kg) effectively inhibits tissue AC activity in multiple organs, including lung, heart, kidney, brain hippocampus, and liver (by 70%, 60%, 44%, 40%, 35%, respectively), with good pharmacokinetic properties (T_max= 30 min,C_max= 1.768 ?g/mL,t_1/2= 458 min, AUC_{0-8 h}= 0.31 mg·min/mL; 10 mg/kg i.p.).

Please note that the molecular weight for this compound is batch-specific due to variable water content. Please refer to the vial label or the certificate of analysis for the batch-specific molecular weight. The molecular weight provided represents the baseline molecular weight without water.
Acid Ceramidase Inhibitor, BOC, CAS 1644158-57-5, is a cell-permeable, potent inhibitor of acid ceramidase (IC?? = 79 nM against HEK293 lysosomal lysate AC activity).

生化/生理作用

Cell permeable: yes
Reversible: no
Primary Target
Acid ceramidase
Target IC₅₀: 79 nM against HEK293 lysosomal lysate AC activity

警告

Toxicity: Standard Handling (A)

重悬

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

其他说明

Pizzirani, D., et al. 2015.Angew. Chem. Int. Ed. Engl.54,485.

法律信息

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

基本信息

经验(实验)分子式	C24H21FN2O3
分子量	404.43

半岛bd体育手机客户端 性质

质量水平	100
测定	≥98% (HPLC)
形式	solid
manufacturer/tradename	Calbiochem?
储存条件	OK to freeze protect from light
颜色	off-white
溶解性	DMSO: 40 mg/mL
储存温度	2-8℃

安全信息

储存分类代码	11 - Combustible Solids
WGK	WGK 3
闪点(F)	Not applicable
闪点(C)	Not applicable