Sigma-Aldrich Acid Ceramidase Inhibitor

Assay

≥98% (HPLC)

Quality Level

100

Form

solid

Manufacturer/Tradename

Calbiochem^®

Storage Condition

OK to freeze
protect from light

Color

off-white

Solubility

DMSO: 40 mg/mL

Storage Temp.

2-8°C

General Description

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 µM). 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 µg/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 µM). 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 µg/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 (IC₅₀ = 79 nM against HEK293 lysosomal lysate AC activity).

Biochem/Physiol Actions

Cell permeable: yesPrimary Target
Acid ceramidaseReversible: noTarget IC₅₀: 79 nM against HEK293 lysosomal lysate AC activity

Warning

Toxicity: Standard Handling (A)

Reconstitution

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

Other Notes

Pizzirani, D., et Al. 2015.Angew. Chem. Int. Ed. Engl. 54,485.CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany