| Identification | Back Directory | [Name]
Ethanone, 1-[(3S)-3-amino-1-pyrrolidinyl]-2-[[(1R,2S)-2-[3,5-difluoro-2-(phenylmethoxy)phenyl]cyclopropyl]amino]-, hydrochloride (1:1) | [CAS]
2262489-89-2 | [Synonyms]
S2116
Ethanone, 1-[(3S)-3-amino-1-pyrrolidinyl]-2-[[(1R,2S)-2-[3,5-difluoro-2-(phenylmethoxy)phenyl]cyclopropyl]amino]-, hydrochloride (1:1) | [Molecular Formula]
C22H26ClF2N3O2 | [MOL File]
2262489-89-2.mol | [Molecular Weight]
437.92 |
| Hazard Information | Back Directory | [Uses]
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[1]. | [Biological Activity]
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[1].
S2116 is particularly effective for T-ALL cell lines with the IC50 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].
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 T1/2 of 3.76 hours, a Cmax of 12.7 μM and an AUC of 59.2 μM?h[1]. | [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[1].
S2116 (50 mg/kg; IP) has a T1/2 of 3.76 hours, a Cmax 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.
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| Animal Model: | 8-week-old ICR mice[1] | | Dosage: | 50 mg/kg (Pharmacokinetic Analysis) | | Administration: | IP | | Result: | Had a T1/2 of 3.76 hours, a Cmax of 12.7 μM and an AUC of 59.2 μM?h.
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Store at -20°C | [References]
[1]. Shiori Saito, et al. Eradication of Central Nervous System Leukemia of T-Cell Origin With a Brain-Permeable LSD1 Inhibitor. Clin Cancer Res. 2019 Mar 1;25(5):1601-1611. |
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