product name SP2509
Description: SP2509 is a selective histone demethylase LSD1 inhibitor with IC50 of 13nM, showing no activity against MAO-A, MAO-B, lactate dehydrogenase and glucose oxidase. SP-2509 showed high actitivity on human AML cells. Treatment with the novel LSD1 antagonist SP2509 attenuated the binding of LSD1 with the corepressor CoREST, increased the permissive H3K4Me3 mark on the target gene promoters, and increased the levels of p21, p27 and CCAAT/enhancer binding protein α in cultured AML cells.
References: Leukemia. 2014 Nov;28(11):2155-64.
437.90
Formula
C19H20ClN3O5S
CAS No.
1423715-09-6
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 38 mg/mL (86.8 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
10% DMSO+corn oil: 5mg/mL
Synonyms
HCI-2509
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19428448
| In Vitro |
In vitro activity: 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. Kinase Assay: Test compounds were diluted to 20 × the desired test concentration in 100% dimethyl sulfoxide and 2.5 μl of the diluted drug sample was added to a black 384-well plate. The LSD1 enzyme stock was diluted 17-fold with assay buffer and 40 μl of the diluted LSD1 enzyme was added to the appropriate wells. Substrate, consisting of horseradish peroxidase, dimethyl K4 peptide corresponding to the first 21 amino acids of the N-terminal tail of histone H3, and 10-acetyl-3,7-dihydroxyphenoxazine was then added to wells. Resorufin was analyzed on a plate reader with an excitation wavelength of 530 nm and an emission wavelength of 595 nm. Cell Assay: 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. |
|---|---|
| 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. |
| Animal model | NOD/SCID mice bearing OCI-AML3 xenografts |
| Formulation & Dosage | Formulated in 20% Cremaphor, 20% DMSO, 60% sterile water; 25 mg/kg; i.p. injection |
| References | Leukemia. 2014 Nov;28(11):2155-64. |
