MMRi6 is aMdm2-MdmX RINGdomain inhibitor that can disruptMdm2-MdmX RING-RINGinteraction in vitro. MMRi6 inhibits MdmX-stimulatedMdm2autoubiquitination and Mdm2-MdmX-mediatedp53polyubiquitination in vitro without affecting NEDD4-1 autoubiquitination. MMRi6 inducesp53stabilization and accumulation and inducesPARPcleavage in wt-p53Emu-myc lymphoma cells. MMRi6 inhibits the growth of wt-p53andp53-null Emu-myc lymphoma cells withIC50sof approximately 0.5 μM and 3 μM, respectively. MMRi6 can be used for the study of leukemia/lymphoma[1].
References:
[1].Wu W, et al. Targeting RING domains of Mdm2-MdmX E3 complex activates apoptotic arm of the p53 pathway in leukemia/lymphoma cells. Cell Death Dis. 2015 Dec 31;6(12):e2035.
MMRi6 是一种Mdm2-MdmX RING结构域抑制剂，可在体外破坏Mdm2-MdmX RING-RING相互作用。MMRi6 在体外抑制 MdmX 刺激的Mdm2自我泛素化和 Mdm2-MdmX 介导的p53多聚泛素化，但不影响 NEDD4-1 的自我泛素化。MMRi6 在 wt-p53Emu-myc 淋巴瘤细胞中诱导p53稳定和积累，并诱导PARP裂解。MMRi6 抑制 wt-p53和p53-null Emu-myc 淋巴瘤细胞的生长，IC50值分别为约 0.5 μM 和 3 μM。MMRi6 可用于白血病/淋巴瘤研究。