XMU-MP-1 是一种促凋亡、无菌的 20 样激酶 MST1 和 2 的抑制剂。

XMU-MP-1 is an inhibitor of the pro-apoptotic, sterile 20-like kinases MST1 and 2.

XMU-MP-1 reduces the phosphorylation of endogenous MOB1, LATS1/2, and YAP in HepG2 cells in a dose-dependent manner at concentrations ranging from 0.1 to 10 μM. XMU-MP-1 treatment inhibits hydrogen peroxide-stimulated MOB1 phosphorylation and MST1/2 autophosphorylation in a variety of cell lines, including mouse macrophage-like cells, human osteosarcoma, human colorectal adenocarcinoma cells. XMU-MP-1 blocks MST1/2 kinase activities, thereby activating the downstream effector Yes-associated protein and promoting cell growth. XMU-MP-1 can potently and reversibly suppress the activities of kinases MST1/2 and enhance their downstream YAP activation in cells.

XMU-MP-1 displays excellent in 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 treatment exhibited substantially greater repopulation rate of human hepatocytes in the Fah-deficient mouse model than in the vehicle-treated control, indicating that XMU-MP-1 treatment might facilitate human liver regeneration. Thus, the pharmacological modulation of MST1/2 kinase activities provides a novel approach to potentiate tissue repair and regeneration, with XMU-MP-1 as the first lead for the development of targeted regenerative therapeutics.

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].

2061980-01-4

C17H16N6O3S2

416.47

DMSO:30 mg/mL
Powder: -20°C for 3 years
In solvent: -80°C for 2 years