Table 1.
Summary of some of the selected inhibitors targeting ceramide-metabolizing enzymes and their mechanism of action.
| Enzyme | Inhibitors | Mechanism of Action and Binding Characteristics | Ref # |
|---|---|---|---|
| Acid Ceramidase |
 (Carmoflur) |
Carmoflur decreases the growth of glioblastoma cell lines and cells isolated from glioblastoma-patient-derived xenografts. It covalently binds to the active site of ASAH1 to inhibit its function, resulting in increased C14:0, C16:0, and C18:0 ceramide. | [185] |
| Acid Ceramidase |
 (Fenretinide) |
Fenretinide treatment results in a cellular ceramide increase in tumor cells. The MOA involves ROS accumulation, cytochrome C release from mitochondrial membrane resulting in mitochondrial membrane depolarization, and cell apoptosis. | [186] |
| Sphingomyelin synthase |
 (jaspine B) |
In vitro studies in cancer cells demonstrated that mitochondrial membrane bound cytochrome C release, resulting in apoptosis. | [187] |
| Sphingosine Kinase |
 (ABC294640) |
Sphingosine Kinase II specific competitive inhibitor. SphKII binding models suggest ABC294640 binding in a J-channel of the active site. | [188] |
| Sphingosine Kinase II |
 (SG-12) |
SG-12 is a synthetic analogue of sphingosine that acts as an SKII inhibitor. It induces apoptosis via phosphorylation by SKII. | [72] |
| Sphingosine Kinase II |
 (FTY720-OMe) |
(R)-FTY720-OMe helps block DNA synthesis and actin rearrangement induced by sphingosine 1-phosphate (S1P) in MCF-7 breast cancer cells. It can also reduce sphingosine kinase 2 (SK2) expression and prevent DNA synthesis in HEK 293 cells. | [73] |
| Sphingosine Kinase II |
 (K145) |
Apoptotic effects in U937 cells, possibly through inhibition of the phosphorylation of downstream RK and Akt signaling pathways. | [74] |
| Sphingosine Kinase I |
 (PF—543) |
Despite being SK1 selective, PF-543 demonstrates poor anticancer activity in several cancer cells. | [189] |
| Dihydroceramide desaturase |
 (Curcumin) |
In a model of lipid trafficking impairment in C6 glial cells, curcumin stimulated ceramide synthesis by increasing the intracellular concentration of ceramide-dihydroceramide. | [190] |
| Dihydroceramide desaturase |
 (XM462) |
Inhibition studies in rat liver microsomes proved XM462 as mixed type inhibitor by a dose dependent inhibition of DES1. | [191] |
| Dihydroceramide desaturase |
 (GT11) |
A Cyclopropene ring mimics the ceramide double bond, the natural 2S,3R stereochemistry, a free hydroxyl group, amide, and alkyl chains. | [191] |