SE-7552, a derivative of 2-(difluoromethyl)-1,3,4-oxadiazole (DFMO), serves as an orally active, highly selective non-hydroxamate HDAC6 inhibitor, boasting an IC50 of 33 nM. It exhibits over 850-fold selectivity against all other known HDAC isozymes. Demonstrating efficacy in vivo, SE-7552 effectively inhibits the growth of multiple myeloma. Additionally, it functions as an anti-obesity agent in diet-induced obese mice [1] [2].

HDAC6:33 nM

SE-7552（30 mg/kg；单次口服）在小鼠体内显著提升α-微管蛋白的乙酰化水平，效果持续超过24小时。同时，SE-7552对H3蛋白的乙酰化（反映I类HDAC抑制的生物标志物）未产生影响[1]。此外，每日口服SE-7552（10 mg/kg）与每日腹腔注射泊马度胺（1 mg/kg）联合治疗，能在携带人类H929 MM细胞的小鼠模型中显著延缓肿瘤生长，并提高存活率[1]。关于药代动力学（PK）方面，SE-7552在小鼠中的表现优异，单次口服剂量为5 mg/kg时，最大药物暴露量达到597 ng/ml，半衰期为7.2小时[1]。