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In vitro: In AML cells, SP2509 inhibits the association of LSD1 with CoREST, increases promoter-specific H3K4Me3 and induces p53, p21 and C/EBPα. SP2509 also significantly inhibits the colony growth and induces apoptosis of OCI-AML3. In addition, SP2509 induces differentiation of cultured and primary AML cells, and exerts synergistic lethal activity when used in combination with panobinostat.
In vivo: In mice bearing OCI-AML3 xenografts, SP2509 (25 mg/kg i.p.) significantly improved the survival of the mice, while co-treatment with SP2509 and panobinostat exerts superior in vivo activity.
| Cell Experiment | |
|---|---|
| Cell lines | OCI-AML3, MV4-11 and MOLM13 cells |
| Preparation method | Cultured AML cells are treated with SP2509 and/or PS for 96 h. At the end of treatment, cells are washed free of the drugs and 500 cells per condition are plated in methylcellulose and incubated at 37 °C. Colony formation is measured 7–10 days after plating. |
| Concentrations | ~10 μM |
| Incubation time | 96 h |
| Animal Experiment | |
|---|---|
| Animal models | NOD/SCID mice bearing OCI-AML3 xenografts |
| Formulation | 20% Cremaphor, 20% DMSO, 60% sterile water |
| Dosages | 25 mg/kg twice per week |
| Administration | i.p. |
| Molecular Weight | 437.90 |
| Formula | C19H20ClN3O5S |
| CAS Number | 1423715-09-6 |
| Solubility (25°C) | 38 mg/mL in DMSO |
| Storage | 2-8°C, protect from light |
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