SP-2577(Seclidemstat), an inhibitor of lysine-specific demthylase KDM1A (LSD1) that is overexpressed in pediatric sarcomas, was evaluated against pediatric sarcoma xenografts. SP-2577 (100 mg/kg/day × 28 days) statistically significantly (p < .05) inhibited growth of three of eight Ewing sarcoma (EwS), four of five rhabdomyosarcoma (RMS), and four of six osteosarcoma (OS) xenografts. The increase in EFS T/C was modest (<1.5) for all models except RMS Rh10 (EFS T/C = 2.8). There were no tumor regressions or consistent changes in dimethyl histone H3(K4), HOXM1, DAX1, c-MYC and N-MYC, or tumor histology/differentiation. SP-2577 has limited activity against these pediatric sarcoma models at the dose and schedule evaluated.

中文翻译：

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赖氨酸特异性去甲基酶 (KDM1A/LSD1) 抑制剂 SP-2577 (Seclidemstat) 针对儿科肉瘤临床前模型的体内评估：来自儿科临床前测试联盟 (PPTC) 的报告

SP-2577（Seclidemstat）是一种在儿科肉瘤中过度表达的赖氨酸特异性脱甲基酶 KDM1A (LSD1) 的抑制剂，针对儿科肉瘤异种移植物进行了评估。SP-2577（100 mg/kg/天 × 28 天）具有统计显着性 ( p  < .05) 抑制八种尤文肉瘤 (EwS) 中的三种、五种横纹肌肉瘤 (RMS) 中的四种和六种骨肉瘤 (OS) 中的四种的生长异种移植物。除了 RMS Rh10 (EFS T/C = 2.8) 之外，所有模型的 EFS T/C 增加幅度不大 (<1.5)。肿瘤消退或二甲基组蛋白 H3(K4)、HOXM1、DAX1、c-MYC 和 N-MYC 或肿瘤组织学/分化没有一致变化。在评估的剂量和时间表下，SP-2577 对这些儿童肉瘤模型的活性有限。