EZM 2302 is a kind of potent and selective inhibitor of CARM1 with an IC50 value of 6nM [1]. EZM 2302 stabilizes an inactive CARM1-S-adenosylhomocysteine (SAH) complex, thereby preventing substrate access and inhibiting methyltransferase activity [1].
EZM 2302 (0~5μM; 96h) led to a concentration-dependent decrease in methylation of PABP1 in the multiple myeloma cell line RPMI-8226; EZM 2302 (0~10μM; 6d) inhibited the proliferation of multiple hematopoietic cell lines [1].
EZM 2302 (37.5, 75, 150 and 300mg/kg; 21d; bid; p.o.) showed significant decreases in tumor growth in CB-17 SCID mice which bore subcutaneous RPMI-8226 xenografts [1]. EZM 2302 (50mg/kg; 11d; i.g.) significantly reduced asymmetrically dimethylated PABP1Arg455/460 content and PABP1 methylation status in C57BL6J/129 mice; EZM 2302 (50mg/kg; 11d; i.g.) decreased the exercise capacity and muscular endurance of male C57BL6J/129 mice [2].
References:
[1] Drew A E, Moradei O, Jacques S L, et al. Identification of a CARM1 inhibitor with potent in vitro and in vivo activity in preclinical models of multiple myeloma [J]. Scientific reports, 2017, 7(1): 17993.
[2] Webb E K, Ng S Y, Mikhail A I, et al. Impact of short-term, pharmacological CARM1 inhibition on skeletal muscle mass, function, and atrophy in mice [J]. American journal of physiology Endocrinology and metabolism, 2023, 325(3): 252-266.
EZM 2302是一种对CARM1有效的且具有选择性的抑制剂，其IC50值为6nM[1]。EZM 2302能通过稳定不活跃的CARM1-S-腺苷基高半胱氨酸（SAH）复合体，从而阻止底物进入并抑制甲基转移酶的活性[1]。
EZM 2302（0~5μM；96h）使多发性骨髓瘤细胞系RPMI-8226中的PABP1甲基化水平呈浓度依赖性下降；EZM 2302（0~10μM；6d）抑制多种造血细胞系的增殖[1]。
EZM 2302（37.5、75、150和300mg/kg；21d；bid；p.o.）显著抑制了皮下移植了RPMI-8226的CB-17 SCID小鼠体内的肿瘤生长[1]。EZM 2302（50mg/kg；11d；i.g.）显著降低C57BL6J/129小鼠的不对称二甲基化PABP1Arg455/460的含量和PABP1甲基化状态；EZM 2302（50mg/kg；11d；i.g.）降低雄性C57BL6J/129小鼠的运动能力和肌肉耐力[2]。