Opaganib is a proprietary, host-directed, potentially broad-spectrum, first-in-class oral SphK2 selective inhibitor developed by RedHill. Currently, it is the most widely used selective SphK2 inhibitor. Opaganib’s host-directed effects are believed to involve the inhibition of multiple signaling pathways, the induction of autophagy and apoptosis, and the suppression of viral replication through the simultaneous inhibition of three sphingolipid-metabolizing enzymes (SphK2, DES1, and GCS) in human cells.
This review systematically presents the complete trajectory of opaganib, a first-in-class oral selective SphK2 inhibitor, from its molecular target and signaling pathways to its disease applications: Centered on the SphK2/S1P axis, opaganib also inhibits DES1 and GCS to exert multifaceted pharmacological effects in cancer, viral infections, inflammation, and radiation injury. The review also outlines key research and development milestones and the clinical pipeline for opaganib, establishing an integrated research framework of “mechanism-activity-clinical translation” to provide novel therapeutic strategies for major diseases such as cancer, viral infections, inflammation, and radiation injury. The work titled “Therapeutic potential of the sphingosine kinase 2 inhibitor opaganib”, was published on Pharmaceutical Science Advances (published on May 22, 2026).
DOI: 10.1016/j.pscia.2026.100125