safingol

Safingol is a lyso-sphingolipid protein kinase inhibitor. It has the molecular formula C18H39NO2 and is a colorless solid. Medicinally, safingol has demonstrated promising anticancer potential as a modulator of multi-drug resistance and as an inducer of necrosis. The administration of safingol alone has not been shown to exert a significant effect on tumor cell growth. However, preclinical and clinical studies have shown that combining safingol with conventional chemotherapy agents such as fenretinide, vinblastine, irinotecan and mitomycin C can dramatically potentiate their antitumor effects. In phase I clinical trials, it was found to be safe to co-administer with cisplatin, but caused reversible dose-dependent hepatotoxicity.

==Mechanism== The underlying mechanism by which safingol induces cell death is poorly understood. It is believed to exert a variety of inhibitory effects, resulting in a series of cascades that result in accidental necrotic cell death brought about by reactive oxygen species (ROS) and mediated by autophagy. Increased autophagic activity has been associated with increased cellular death, although it is unclear if there is any causative relationship between the two. Because autophagy normally plays a pro-survival role by impeding apoptosis, it is curious that it may play a role in cell death following safingol exposure.