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LCL521

Catalog No. T11835   CAS 1226851-11-1

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

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LCL521 Chemical Structure
LCL521, CAS 1226851-11-1
Pack Size Availability Price/USD Quantity
25 mg 6-8 weeks $ 987.00
50 mg 6-8 weeks $ 1,360.00
100 mg 6-8 weeks $ 2,190.00
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Biological Description
Chemical Properties
Storage & Solubility Information
Description LCL521 inhibits lysosomal acid sphingomyelinase (ASMase).LCL521 is an acid ceramidase (ACDase) inhibitor.
In vitro LCL521 (1 µM) effectively inhibited ACDase in MCF7 cells, but the effects were transient. LCL521 (10 µM) caused a profound decrease of sphingosine and an increase of ceramide, but additionally affected the processing and regeneration of the ACDase protein, with biphasic and reversible effects on the expression of ACDase, which paralleled the long-term changes of cellular sphingosine and ceramide. The higher concentrations of LCL521 also inhibited Dihydroceramide desaturase (DES-1). In summary, LCL521 exhibits significant effects on ACDase in a dose and time-dependent manner.[2]
In vivo When PDT-treated SCCVII cells are used to vaccinate SCCVII tumor-bearing mice, adjuvant LCL521 treatment (75 mg/kg; i.p.) resulted in marked retardation of tumor growth. This effect can be attributed to the capacity of LCL521 to effectively restrict the activity of two main immunoregulatory cell populations (Tregs and myeloid-derived suppressor cells, MDSCs) that are known to hinder the efficacy of PDT vaccines. The interaction of LCL521 with PDT-based antitumor mechanisms is dominated by immune system contribution that includes overriding the effects of immunoregulatory cells but could also include a tacit contribution from boosting direct tumor cell kill.[3]
Molecular Weight 592.77
Formula C31H52N4O7
CAS No. 1226851-11-1

Storage

Powder: -20°C for 3 years | In solvent: -80°C for 1 year

Solubility Information

DMSO: 148.5 mg/mL (250.5 mM), sonification is recommended.

Ethanol: 90.0 mg/mL (151.8 mM), sonification is recommended.

TargetMolReferences and Literature

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. 2. Bai A, et al. Dose dependent actions of LCL521 on acid ceramidase and key sphingolipid metabolites. Bioorg Med Chem. 2018;26(23-24):6067-6075. 3. Korbelik M, et al. Interaction of acid ceramidase inhibitor LCL521 with tumor response to photodynamic therapy and photodynamic therapy-generated vaccine. Int J Cancer. 2016;139(6):1372-1378. 4. Liu F, et al. Ceramide activates lysosomal cathepsin B and cathepsin D to attenuate autophagy and induces ER stress to suppress myeloid-derived suppressor cells. Oncotarget. 2016;7(51):83907-83925. 5. White-Gilbertson S, et al. Polyploid giant cancer cells are dependent on cholesterol for progeny formation through amitotic division. Sci Rep. 2022;12(1):8971. 6. Korbelik M, et al. Mechanistic insights into ceramidase inhibitor LCL521-enhanced tumor cell killing by photodynamic and thermal ablation therapies. Photochem Photobiol Sci. 2020;19(9):1145-1151.

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Keywords

LCL521 1226851-11-1 Metabolism Others Phospholipase LCL-521 LCL 521 inhibitor inhibit

 

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