XI-006 (XI-006) suppresses MDMX with IC50 of 2.5 μM, leading to enhanced p53 stabilization/activation and DNA damage, and also regulates MDM2, an E3 ligase.

MDMX:2.5 μM

XI-006 在MCF-7细胞中降低了MDMX mRNA和蛋白的表达，并以剂量依赖性的方式促进了p53及其靶基因p21和MDM2的表达。此外，XI-006通过环己亚胺追踪实验将p53的半衰期从20到30分钟延长至超过3小时。在LNCaP前列腺癌细胞和A549肺癌细胞中，XI-006同样激活了p53并诱导了p21和MDM2的表达。XI-006还能提高MCF-7细胞中包括PUMA、BAX和PIG3在内的促凋亡基因的mRNA水平。此化合物导致了显著增加的亚G0/G1细胞数量和G2期阻滞，并在A549和LNCaP细胞中通过诱导超过40%的细胞凋亡降低了细胞活性。[1] XI-006在L1210细胞中抑制了核酸和蛋白质的生物合成。[2] XI-006通过与DNA修复相互作用激活了三种物种（S. cerevisiae、S. pombe和H. sapiens）的DNA损伤修复途径。[3] 在G/R-luc星形胶质瘤细胞系中，XI-006表现出细胞毒性作用，具有117 nM的GI50。[4]

MCF-7 cells treated with dimethyl sulfoxide (DMSO), nutlin-3a, or NSC-207895 are permeabilized with cold 70% ethanol overnight, and stained with a solution containing 50 μg/mL propidium iodide and 20 μg/mL RNase A at 37°C for 20 minutes. The cells are then subjected to flow cytometry analysis. The FlowJo software is used to calculate percentages of cells in each cell cycle phase. For terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling (TUNEL) staining, MCF-7 cells treated with the NSC-207895 for 2 days are fixed with 4% paraformadelhyde for 1 hour, and then subjected to dUTP labeling using In Situ Cell Death Detection Kit TMR Red according to the manufacturer's protocol. For quantitation, at least 300 cells are randomly chosen and the numbers of TUNEL-positive cells are counted. (Only for Reference)