产品介绍 SP2509 (HCI-2509)是一种选择性histone demethylase LSD1抑制剂，IC50为 13 nM，对MAO-A，MAO-B，乳酸脱氢酶和葡萄糖氧化酶没有活性。SP2509 可诱导凋亡并促进自噬。参考 产品说明 “高效，选择性和可逆的组蛋白脱甲基酶LSD1抑制剂 “改为 “有效的，选择性的和可逆的组蛋白脱甲基酶LSD1拮抗剂” 添加产品介绍SP2509是一种新型的赖氨酸特异性去甲基化酶1（LSD1）拮抗剂，IC50值为13 nM，对MAO-A和MAO-B不起作用。 LSD1对组蛋白H3上的单/二甲基化赖氨酸4进行去甲基化。LSD1的高表达与癌症的预后不良相关。在培养的人急性髓细胞性白血病（AML）细胞中，SP2590抑制LSD1的活性，抑制集落生长，诱导细胞凋亡。SP2590也可以抑制LSD1与CoREST的结合，增加启动子特异性的H3K4Me3，诱导p53、p21和C/EBPα。而且，SP2590还可以促进培养的和原代的AML细胞的分化。 在AML异种移植小鼠中，SP2590单独治疗显著提高了小鼠的存活率，与HDAC的抑制剂panobinostat (PS)共同治疗时具有很好的体内活性。 product description： A cell-permeable, lysine-specific demethylase 1 (LSD1) active site-targeting phenethylidene-benzohydrazide that inhibits LSD1 activity (IC50 = 13 nM) in a reversible and substrate non-competitive (Ki = 34 nM) manner, while inhibiting CYP3A4 only at much higher concentrations (IC50 = 2.61 µM) and displaying little or no potency towards CYP1A2/2C9/2C19/2D6. MAO-A/B, D-lactate dehydrogenase, glucose oxidase, and hERG (IC50 ≥8.0 µM). Shown to enhance histone H3 Lys9 dimethylation (H3K9me2) in androgen-dependent prostate cancer VCaP cultures (1 to 10 µM) and effectively inhibits LSD1-dependent cancer growth (IC50 in nM = 329/SK-N-MC, 356/AN3 Ca, 429/HT29, 468/MIA PaCa-2, 489/BT-20, 612/HER218, 614/HCT 116, 637/MCF-7, 649/T-47D; 96 h). A cell-permeable phenethylidene-benzohydrazide compound that acts as a potent, selective, reversible, and non-competitive inhibitor of Lysine-Specific Demethylase 1 (LSD1; IC50 = 13 nM; Ki = 31 nM). Exhibits excellent selectivity over monoamine oxidases A and B (IC50 >300 µM), lactate dehydrogenase, glucose oxidase, hERG, CYP1A2, CYP2D6 (IC50 ≥ 10 µM), CYP2C9 (IC50 = 8.04 µM) and CYP2C19 (IC50 = 9.76 µM). Inhibits CYP3A4 only at >200-fold higher concentration. Reduces the proliferation of several cancer cell lines, including AN3 Ca, BT-20, MCF-7, T-47D, HT29, MIA PaCa-2 and SK-N-MC (IC50 = 356, 489, 637, 649, 429, 468 and 329 nM, respectively).