S2116 is a powerful inhibitor of lysine-specific demethylase 1 (LSD1), and it is a derivative of N-alkylated tranylcypromine (TCP). S2116 exhibits its inhibitory effects by increasing H3K9 methylation and inducing reciprocal H3K27 deacetylation at super-enhancer regions. In TCP-resistant T-cell acute lymphoblastic leukemia (T-ALL) cells, S2116 triggers apoptosis by repressing the transcription of NOTCH3 and TAL1 genes. Furthermore, S2116 demonstrates significant growth retardation of T-ALL cells when xenotransplanted into mice.

S2116 is particularly effective for T-ALL cell lines with the IC 50 values between 1.1 μM for human T-ALL cell lines CEM and 6.8 μM for MOLT4[1]. S2116 (4-20 μM; 72 hours) modestly inhibits mitogen-activated normal T-lymphocytes[1]. S2116 (4-8 μM; 24 hours) induces apoptosis and down-regulates the expression of NOTCH3 and TAL1 proteins in T-ALL cells[1]. Cell Viability Assay[1]Cell Line: Normal T-lymphocytes Concentration: 4, 8, 12, 16, 20 μM Incubation Time: For 72 hours Result: Modestly inhibited mitogen-activated normal T-lymphocytes. Apoptosis Analysis[1]Cell Line: T-cell acute lymphoblastic leukemia (T-ALL) cells Concentration: 4, 6, 8 μM Incubation Time: For 24 hours Result: Induced apoptosis, as evidenced by increased annexin-V reactivity on flow cytometry in T-ALL cells in a dose- and time-dependent manner without affecting cell cycle distribution. Western Blot Analysis[1]Cell Line: T-ALL cells Concentration: 4, 6, 8 μM Incubation Time: For 24 hours Result: Down-regulated the expression of NOTCH3 and TAL1 proteins in T-ALL cells.

S2116 (50 mg/kg; IP; 3 times a week; for 28 days) causes the size of subcutaneous tumors reduced to less than 20% of that in the untreated control[1]. S2116 (50 mg/kg; IP) has a T 1/2 of 3.76 hours, a C max of 12.7 μM and an AUC of 59.2 μM?h[1]. Animal Model: Nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice with MOLT4 cells[1]Dosage: 50 mg/kg Administration: IP; 3 times a week; for 28 days Result: The size of subcutaneous tumors reduced to less than 20% of that in the untreated control. Animal Model: 8-week-old ICR mice[1]Dosage: 50 mg/kg (Pharmacokinetic Analysis) Administration: IP Result: Had a T 1/2 of 3.76 hours, a C max of 12.7 μM and an AUC of 59.2 μM?h.