Table 2.
List of anticancer drugs targeting sphingolipid metabolism
| Name | Target or activity | Stage of development | Refs |
|---|---|---|---|
| Ceramide inducers and analogues | |||
| C8-CPC | DES | Preclinical | 43 |
| CHC | CERT; ceramide trafficking; sphingomyelin synthesis | Preclinical | 56 |
| NVP-231 | CERK | Preclinical | 59 |
| LCL521 and LCL204 | AC | Preclinical | 66–68 |
| Pyridinium ceramide (LCL-124 and LCL-461) | Cancer mitochondria and/or mitophagy | Preclinical | 152,153 |
| Nanoliposomal ceramide | Survivin | Preclinical | 154 |
| Inhibitors of S1P metabolism and signalling | |||
| FTY720 | S1PR1; I2PP2A | FDA-approved (for multiple sclerosis) | 91, 148–150 |
| JTE013 | S1PR2 | Preclinical | 107 |
| AB1 | S1PR2 | Preclinical | 161 |
| SK1-I | SPHK1 | Preclinical | 156 |
| PF543 | SPHK1 | Preclinical | 157–159 |
| VPC03090 | S1PR1; S1PR3 | Preclinical | 160 |
| Sphingomab (sonepcizumab) | S1P | Phase II | 162 |
| ABC294640 | SPHK2; DES | Phase Ib and II | 163–170 |
AC, acid ceramidase; C8-CPC, C8-cyclopropenylceramide; CERK, ceramide kinase; CERT, ceramide transfer protein; CHC, 3-chloro-8β-hydroxycarapin-3,8-hemiacetal; DES, dihydroceramide desaturase; FDA, US Food and Drug Administration; I2PP2A, phosphatase 2A inhibitor I2PP2A; S1P, sphingosine-1-phosphate; S1PR, S1P receptor; SPHK, sphingosine kinase.