Wip1(PPM1D)的抑制剂;an inhibitor of Wip1 (PPM1D);CCT007093是一种有效的PPM1D抑制剂,可选择性降低人类肿瘤细胞系的生存能力。PPM1D是一种磷酸酶,其基因在一系列常见癌症中异常扩增。PPM1D激活通过P38激酶的选择性失活导致P53功能的负调控。因此,该酶可以被认为是潜在的癌症治疗靶标。本研究确定了一种化合物CCT007093,该化合物通过抑制这种磷酸酶来选择性降低过表达PPM1D的人类肿瘤细胞系的生存能力。CCT007093的独特优势在于它能够模仿基因特异性PPM1D RNAi的作用,不仅具有对过表达PPM1D的人类肿瘤细胞的选择性,而且还;CCT007093 is an effective PPM1D inhibitor that selectively reduces viability of human tumour cell lines. PPM1D is a phosphatase where the gene which is aberrantly amplified in a range of common cancers. PPM1D activation results in negative regulation of P53 function by selective inactivation of P38 kinase. Therefore, this enzyme can be considered as a potential therapeutic target for cancer. The present study identified a compound, CCT007093 that selectively reduces viability of human tumour cell lines overexpressing PPM1D through inhibition of this phosphatase. The unique advantage of CCT007093 is its ability to mimic the effects of gene-specific PPM1D RNAi, both in its selectivity for human tumour cells that overexpress PPM1D and also by its reliance on an integral P38 pathway.
体内研究:
CCT007093 (6.4 mg/kg) enhances liver regeneration and increases the survival rate of mice following major hepatectomy.