S2116, a N-alkylated tranylcypromine (TCP) derivative, is a potent lysine-specific demethylase 1 (LSD1) inhibitor. S2116 increases H3K9 methylation and reciprocal H3K27 deacetylation at super-enhancer regions. S2116 induces apoptosis in TCP-resistant T-cell acute lymphoblastic leukemia (T-ALL) cells by repressing transcription of the NOTCH3 and TAL1 genes. S2116 significantly retardes the growth of T-ALL cells in xenotransplanted mice
In Vitro
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. S2116 (4-20 µM; 72 hours) modestly inhibits mitogen-activated normal T-lymphocytes. S2116 (4-8 µM; 24 hours) induces apoptosis and down-regulates the expression of NOTCH3 and TAL1 proteins in T-ALL cells. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Cell Viability AssayCell 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 AnalysisCell 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 AnalysisCell 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.
In Vivo
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 . 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 . MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: Nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice with MOLT4 cells 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 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.
