ABC294640 [(1s,3r,5R,7S)-3-(4-chlorophenyl)-N-(pyridin-4-ylmethyl)adamantane-1-carboxamide] is a first-in-class orally-available inhibitor of Sphingosine Kinase-2 (SK2) that has activity both as a single-agent and in drug combinations in models of liver, kidney, pancreas, breast, ovary, colon and lung cancer, as well as leukemia and multiple myeloma.
ABC294640 inhibits SK2, a lipid kinase that catalyzes formation of the lipid signaling molecule sphingosine 1-phosphate (S1P). S1P promotes cancer growth, and proliferation and pathological inflammation, including TNFa signaling and other inflammatory cytokine production. Specifically, by inhibiting the SK2 enzyme, ABC294640 blocks the synthesis of S1P which regulates fundamental biological processes such as cell proliferation, migration, immune cell trafficking and angiogenesis, and are also involved in immune-modulation and suppression of innate immune responses from T cells. Preliminary evidence suggests that because of its specificity for targeting SK2, rather than SK1, ABC294640 may have a better therapeutic ratio than nonspecific sphingosine kinase inhibitors or those targeting only SK1.
ABC294640 is developed by Apogee Biotechnology. RedHill Biopharma have an exclusive worldwide license agreement under which RedHill has acquired the rights to the Phase II drug candidate ABC294640 and additional intellectual property rights.
