SPT-IN-2

SPT-IN-2 is an orally active serine palmitoyltransferase ( SPT ) inhibitor (with an IC₅₀ of 0.71 nM against human SPT2 ). SPT-IN-2 inhibits ceramide synthesis, suppresses cancer cell growth, and exhibits in vivo anti-tumor activity, favorable metabolic stability and cell membrane permeability in xenograft mouse models. SPT-IN-2 blocks the de novo sphingolipid synthesis pathway, significantly reducing intracellular ceramide levels and the levels of 3-ketodihydrosphingosine (3-KDS), the immediate downstream product of SPT. SPT-IN-2 can be used in research related to lung adenocarcinoma, acute promyelocytic leukemia and breast cancer ^[1].

In Vivo, SPT-IN-2 (compound 5) (10 mg/kg, 30 mg/kg; oral administration by gavage; Q2D; 2 weeks) exhibits significant in vivo anti-tumor activity in a xenograft mouse model of human acute promyelocytic leukemia PL-21 cells, effectively inhibits the in vivo growth of xenograft tumors, and causes no obvious toxic side effects such as severe body weight loss in mice during the administration period^[1].

In Vitro, SPT-IN-2 (compound 5) (IC₅₀ 4.1 nM; 5 d) exerts potent antiproliferative effects on human acute promyelocytic leukemia PL-21 cells, with a 95% confidence interval of 3.4-4.7 nM^[1].

References:
[1]. Kojima T, et al. Discovery of novel serine palmitoyltransferase inhibitors as cancer therapeutic agents. Bioorg Med Chem. 2018;26(9):2452-2465.