SACLAC is an irreversible inhibitor of acid ceramidase (Ki = 97.1 nM) and a derivative of the acid ceramidase inhibitor SABRAC .1 It decreases levels of sphingosine-1-phosphate (S1P) and increases total ceramide levels in OCI-AML-2 acute myeloid leukemia (AML) cells when used at a concentration of 2.5 µM.2 SACLAC (10 and 20 µM) induces apoptosis in primary AML cells. It reduces leukemic burden in MV4-11 and U937 AML mouse xenograft models when administered at a dose of 5 mg/kg.
1.OrdÓÑez, Y.F., Abad, J.L., Aseeri, M., et al.Activity-based imaging of acid ceramidase in living cellsJ. Am. Chem. Soc.141(19)7736-7742(2019) 2.Pearson, J.M., Tan, S.-F., Sharma, A., et al.Ceramide analogue SACLAC modulates sphingolipid levels and MCL-1 splicing to induce apoptosis in acute myeloid leukemiaMol. Cancer Res.18(3)352-363(2020)