SPT inhibitor compound-2 is a potent, orally active serine palmitoyltransferase (SPT) inhibitor with IXC50 of 0.51 nM in cell-free assays.
Compound-2 reduced the intracellular levels of 3-ketosphinganine (3-KDS), C16, C24-Cer, and C16, C24-SM downstream of SPT in a dose-dependent manner in PL-21 cells.
Compound-2 exhibited anti-proliferative effect in PL-21 cells with GI50 of 3.32 nM, reducing the levels of the sphingolipids ceramide and sphingomyelin.
Compound-2 (3 mg/kg, oral) showed potent antitumor activity without causing significant body weight loss in the PL-21 acute myeloid leukemia mouse xenograft model.
