For research use only.
Storage
3 years,-20°C,powder
1 years,-80°C,in solvent
In vitro
XMU-MP-1 blocks MST1/2 kinase activities, thereby activating the downstream effector Yes-associated protein and promoting cell growth. XMU-MP-1 inhibits phosphorylation of MOB1 in a dose-dependent manner. Furthermore, with increasing ATP concentration, XMU-MP-1 exhibits a proportional increase in IC50 against MST1/2, as well as an attenuated inhibition of the MST2-mediated phosphorylation of MOB1. At concentrations ranging from 0.1 to 10 μM, XMU-MP-1 reduces the phosphorylation of endogenous MOB1, LATS1/2, and YAP in human liver carcinoma (HepG2) cells in a dose-dependent manner. Similarly, XMU-MP-1 treatment inhibits hydrogen peroxide (H2O2)-stimulated MOB1 phosphorylation and MST1/2 autophosphorylation in a variety of cell lines, including mouse macrophage-like cells (RAW264.7), human osteosarcoma (U2OS), human colorectal adenocarcinoma (SW480), immortalized human retinal pigment epithelial cells (RPE1), human pleomorphic hepatocellular carcinoma (SNU-423), and HepG2, as well as primary mouse hepatocytes, without affecting the phosphorylation of JNK (c-Jun N-terminal kinase), which is a positive control for H2O2 stimulation. XMU-MP-1 treatment increases YAP nuclear translocation.
In vivo
XMU-MP-1 displays excellent in vivo pharmacokinetics and is able to augment mouse intestinal repair, as well as liver repair and regeneration, in both acute and chronic liver injury mouse models at a dose of 1 to 3 mg/kg via intraperitoneal injection. XMU-MP-1 exhibits favorable pharmacokinetics in rats with a half-life of 1.2 hours and a bioavailability of 39.5%. The maximal phosphorylation inhibition of MOB1 and YAP is achieved between 1.5 and 6 hours after intraperitoneal dosing with XMU-MP-1 (1 mg/kg). XMU-MP-1 protects mice from DSS-induced colitis and ameliorates chronic liver injury.
