XMU-MP-1 is a reversible and selective MST1/2 kinase inhibitor, and its IC50 values for MST1 and MST2 are 71.1 nM and 38.1 nM, respectively.

MST2:38.1 nM, MST1:71.1 nM, MST3:44.8 nM, MST4:27.3 nM, MST2:18.2 nM

METHODS: HepG2 cells, mouse macrophage-like cells, human osteosarcoma, and human colorectal adenocarcinoma cells were treated with XMU-MP-1 (0-3 μM) for 15 minutes, and the phosphorylation levels were detected by western blot.
RESULTS: XMU-MP-1 reduces the phosphorylation of endogenous MOB1, LATS1/2 and YAP in HepG2 cells in a dose-dependent manner. XMU-MP-1 inhibits hydrogen peroxide-stimulated phosphorylation of MOB1 and autophosphorylation of MST1/2 in mouse macrophagocyte-like cells, human osteosarcoma, and human colorectal adenocarcinoma cells. [1]

METHODS: To study the effect of XMU-MP-1 on cardiac function, C57Bl/6 mice underwent transverse aortic cotation (TAC) surgery to induce cardiac hypertrophy and dysfunction. XMU-MP-1 (1 mg/kg) or solvent (DMSO) treatment was administered 3 weeks after the operation, once every 2 days for 10 consecutive days.
RESULTS: The cardiac systolic function of mice treated with XMU-MP-1 was significantly improved, manifested as an increase in ejection fraction. The cross-sectional area of myocardial cells in mice treated with XMU-MP-1 decreased, and the expression of the hypertrophy marker brain natriuretic peptide (BNP) decreased. The number of TunEL-positive cardiomyocytes in the hearts of mice treated with XMU-MP-1 decreased, and the degree of fibrosis was reduced, indicating that this drug inhibited cardiomyocyte apoptosis and fibrosis. [2]
METHODS: To study the ability of XMU-MP-1 in liver injury repair, XMU-MP-1 (1-3 mg/kg) was intraperitoneally injected into mouse models of acute/chronic liver injury.
RESULTS: XMU-MP-1 has good pharmacokinetic characteristics in vivo and can improve the repair and regeneration ability of the intestinal tract and liver of mice.
METHODS: To study the anti-tumor activity of XMU-MP-1, XMU-MP-1 was injected daily into NSG mice supplemented with estrogen.
RESULTS: XMU-MP-1 significantly inhibited tumor growth in MCF-7 xenografts, and the treated xenografts showed increased nuclear localization of YAP and expression of target genes. [3]
METHODS: To study the effect of XMU-MP-1 on osteoarthritis, XMU-MP-1 (1 mg/kg) was intraperitoneally injected into a mouse model of osteoarthritis for two consecutive weeks.
RESULTS: XMU-MP-1 can inhibit the erosion of the articular cartilage surface and the thickening of the synovial membrane, and alleviate the symptoms of osteoarthritis.

XMU-MP-1 is dissolved in DMSO (stock concentration, 10 mM). For the in vitro kinase inhibition assays, recombinant GST-tagged MOB1a and various forms of recombinant His-tagged full-length MST1 or MST2 kinase are expressed and purified from Escherichia coli. The assays are performed with the various doses of XMU-MP-1 in the kinase assay buffer for 30 min at 30°C[1].