5.33371

Acid Ceramidase Inhibitor IV, BOC

• Synonym(s): Acid Ceramidase Inhibitor IV, BOC, AC Inhibitor IV
• Empirical Formula (Hill Notation): C₂₄H₂₁FN₂O₃
• CAS Number: 1644158-57-5
• Molecular Weight: 404.43
• UNSPSC Code: 12352106

Properties

• 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

Description

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 (IC₅₀ with 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 (IC₅₀ with 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: yes

Primary Target
Acid ceramidase

Reversible: no

Target 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.

Legal Information

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

Safety Information

• Storage Class Code: 11 - Combustible Solids
• WGK: WGK 3
• Flash Point(F): Not applicable
• Flash Point(C): Not applicable