Therapeutic potential of the sphingosine kinase 2 inhibitor opaganib

Opaganib is a proprietary, host-directed, potentially broadly potent, first-in-class oral sphingosine kinase 2 (SphK2) selective inhibitor developed by RedHill Biopharma Tel Aviv, Israel. It is currently the most widely used selective SphK2 inhibitor. It simultaneously inhibits three sphingolipid-metabolizing enzymes in human cells-SphK2, dihydroceramide desaturase (DES1), and glucosylceramide synthase (GCS)-leading to depletion of sphingosine 1-phosphate (S1P), accumulation of ceramides and dihydroceramides, and suppression of key pro-survival pathways including pERK, pAKT, and NF-κB. These events promote autophagy, apoptosis, and disruption of viral replication. A large body of evidence indicates that SphK plays an important role in health and disease. This study reviews the role and mechanisms of opaganib effects as anticancer, anti-inflammatory, and antiviral agent. The latest research directions for opaganib are described as gastrointestinal acute radiation syndrome (GI-ARS), chemical exposure indications, and COVID-19, Ebola, and other viruses, providing new therapeutic ideas and considerations for future research and clinical trials.