LCL521 dihydrochloride

LCL521 dihydrochloride is an acid ceramidase (ACDase) inhibitor. LCL521 also inhibits the lysosomal acid sphingomyelinase (ASMase).

Signaling Pathways >> Others >> Others

Research Areas >> Cancer

ACDase, ASMase[1]

Acid ceramidase (ACDase) is being recognized as a therapeutic target for cancer. B13 represents a moderate inhibitor of ACDase. LCL521 applied at a lower concentration, 1 µM, shows an effect similar to 10µM treatment, suggesting a high efficiency on this enzyme inhibition. LCL521 causes a time-dependent decrease of the α-ACDase form. 1 µM LCL521 acts as a potent inhibitor of cellular ACDase activity, whereas 10 µM LCL521 has an additional, decreased affect on the α-form of this enzyme. Moreover, LCL521 acts as inhibitor of the lysosomal ACDase and ASMase[1].

HeLa cells overexpressing ASAH2, ACER2, or empty vector are grown to a 60% confluence before they are treated with Tetracycline (5 ng/mL) overnight. Next day, the cells are then treated with B13 (10 µM), LCL521 (1 or 10 µM), or Ethanol (the vehicle control for both B13 and LCL521) for 1 h before they are harvested[1].

[1]. Bai A, et al. Targeting (cellular) lysosomal acid ceramidase by B13: design, synthesis and evaluation of novel DMG-B13 ester prodrugs. Bioorg Med Chem. 2014 Dec 15;22(24):6933-44.

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