SP2509 - LSD1 Antagonist - 生命科学试剂 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemESP2509Cat. No.: HY-12635CAS No.: 1423715-09-6分式: CHClNOS分量: 437.9作靶点: Histone Demethylase作通路: Epigenetics储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 DMSO : 33 mg/mL (75.36 mM)H2O : 40% PEG300

2、5% Tween-80 45% salineSolubility: 2.08 mg/mL (4.75 mM); Clear solutionBIOLOGICAL ACTIVITY1/3 Master of Small Molecules 您边的抑制剂师www.MedChemE物活性 SP2509是有效，选择性的 LSD1 拮抗剂，IC50 值为 13 nM。IC50 & Target IC50: 13 nM (LSD1) 1体外研究 SP2509 (250, 500, 1000 nM) inhibits LSD1 activity, depletes colony growth and ind

3、uces apoptosis and celldeath of cultured human acute myeloid leukemia cells, and increases H3K4Me3 on the promoters of p57 Kip,KLF4, and p21 and induces mRNA expression of p57Kip, KLF4 and p21 in AML cells. SP2509 (250, 1000nM) induces features of morphologic differentiation of cultured and primary

4、AML cells. Besides, SP2509 incombination with PS exerts synergistic lethal activity against cultured and primary AML cells 1. SP2509does not destabilize the CoREST-LSD1 interaction, and has no major destabilizing effect on the CRC.SP2509 (1 or 10 M) induces cell death, but there are no morphological

5、 changes at a low concertation of 0.1M. SP2509 likewise interferes with the viability of medulloblastoma cells 2.体内研究 Treatment with SP2509 (25 mg/kg) and/or PS (5 mg/kg) significantly enhances PS-mediated loss of viabilityof CD34+ primary AML cells and improves the survival of mice bearing AML xeno

6、grafts and primagrafts 2.PROTOCOLKinase Assay 2 To measure the activity of LSD1, a luminol-based assay is used. A total of 5 L of eluate is diluted in LSD1reaction buffer (50 mM Tris, pH 8.5, 50 mM KCl, 5 mM MgCl2, 5 nmol luminol, 20 g/mL horseradishperoxidase, 1% Triton X-100), and 10 M H3K4me2 (1-

7、21 aa) peptide is added as the substrate. DMSO andinhibitors are added. The total volume per reaction is 100 L. The samples are measured in a white 96-wellplate using an EnSpire multimode plate reader at an emission wavelength of 428 nm. Three individualpurifications (n=3) are used for the assay, wi

8、th three technical replicates for each.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Cell Assay 2 Daoy and D283 Med cells are used in the assay. ONS-76 cells are cultured in RPMI medium 1640supplemented with 10% FBS, 50 U/mL penicillin, and 50 g/mL st

9、reptomycin. All medulloblastoma cell linesare kept in an incubator at 37C in a 5% CO2/5% O2/90% N2 atmosphere with maximum humidity. XTTassays are performed in triplicates (n=3) with three replicates for each using 1103 Daoy cells/well, 4103D283 Med cells/well, and 1103 ONS-76 cells/well in 100 L of

10、 medium at initial seeding in 96-well plates.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Female NOD/SCID mice are exposed to 2.5 Gy of radiation. The following day, 5 million OCI-AmL3 cells areAdministration 1 injected into the lateral tail v

11、ein of the mice and the mice are monitored for 7 days. Following treatments areadministered in cohorts of 8 mice for each treatment: vehicle alone, 25 mg/kg SP2509, 5 mg/kg panobinostatand SP2509 plus panobinostat. Treatments are initiated on day 7 for OCI-AmL3 cells. SP2509 (formulated insolubiliza

12、tion buffer 20% Cremaphor, 20% DMSO, 60% sterile water) is administered twice per week (Tuesand Thurs) intraperitoneally (IP) for 3 weeks, and then discontinued. Panobinostat (formulated in 5% DMSO/95% normal saline) is administered by IP injection 3 days per week (M-W-F) for 3 weeks and discontinue

13、d.The doses of PS utilized in these studies are determined to be safe and effective. A separate in vivoexperiment is conducted utilizing NSG mice and primary AmL cells. Following engraftment of the AmL cells(presence of greater than 1% CD45+ cells in the peripheral blood), mice are treated with SP25

14、09 and/or PS,2/3 Master of Small Molecules 您边的抑制剂师www.MedChemEfor three weeks.MCE has not independently confirmed the accuracy of these methods. They are for reference only.户使本产品发表的科研献 Acta Pharm Sin B. 2019 Mar;9(2):324-334. Oncotarget. 2017 Aug 10;8(43):74434-74450.See more customer validations on

15、 HYPERLINK / www.MedChemEREFERENCES1. Fiskus W, et al. Highly effective combination of LSD1 (KDM1A) antagonist and pan-histone deacetylase inhibitor against human AMLcells. Leukemia. 2014 Nov;28(11):2155-64.2. Inui K, et al. Stepwise assembly of functional C-terminal REST/NRSF transcriptional repressor complexes as a drug targe