The mammalian ste20-like kinases 1/2 (MST1/2) which is a core component in the Hippo pathway in mammals, is related in cell growth, controlling organ size and maintaining organ homeostasis[1]. XMU-MP-1 is a potent and selective inhibitor of MST1/2 with IC50 value of 71.1 nM and 38.1 nM against MST1 and MST2, respectively[2]. XUM-MP-1 was added to a variety of cell lines including RAW264.7, USOS, SW480, SNU-423, RPE1 and HepG2, and the inhibition of hydrogen peroxide (H2O2)–stimulated MOB1 phosphorylation and MST1/2 autophosphorylation started at concentration of 1 and 3 μM for all cell lines measured by immunoblotting assay after incubating with XMU-MP-1 for 3 hours. In Sprague-Dawley rats, after intraperitoneal administration of 1 mg/kg XMU-MP-1, the maximal phosphorylation inhibition of MOB1 and YAP was achieved between 1.5 and 6 hours in the liver tissue. The wild-type mice were treated with XMU-MP-1 once a day before a two-thirds partial hepatectomy followed by daily treatment for 7 days. The treatment of XMU-MP-1 could enhance liver regeneration and increase the amounts of Ki67-positive cells and YAP-positive cells in the liver, as well as liver/body weight ratio compared with the control group.
作用机制
XMUMP-1 target the ATP-binding site of the kinases MST1/2.
XMU-MP-1 细胞实验
Cell Line
Concentration
Treated Time
Description
References
LX-2 cells
5 µM
24 h
Block the Hippo signaling pathway and attenuate the inhibitory effect of ADMSCs on HSCs
Stem Cell Res Ther. 2024 Oct 24;15(1):378.
C2C12 cells
1 μM
6 h
Restores YAP/TAZ nuclear localization in BAG3-depleted cells
Biomaterials. 2021 Oct;277:121097.
NSCLC cell lines H1299
1 mM
24 h
XMU-MP-1 treatment partially reversed ACADL-induced YAP phosphorylation and promoted nuclear accumulation of YAP.
Cancer Cell Int. 2024 Feb 24;24(1):86.
NSCLC cell lines A549
1 mM
24 h
XMU-MP-1 treatment partially reversed ACADL-induced YAP phosphorylation and promoted nuclear accumulation of YAP.
Cancer Cell Int. 2024 Feb 24;24(1):86.
BMDMs
3μM
6 h
After inhibiting MST1/2 activity, RNA-Seq and qRT-PCR results showed increased expression of inflammatory cytokines under LPS stimulation and decreased expression of M2 markers under IL-4+IL-13 stimulation.
Int J Biol Sci. 2024 Jan 12;20(3):1004-1023.
RAW 264.7
5μM
4-6 h
After pretreatment with XMU-MP-1, RAW 264.7 cells showed inhibited MST1/2 activity and changes in Hippo pathway-related protein expression under LPS or IL-4+IL-13 stimulation.
Int J Biol Sci. 2024 Jan 12;20(3):1004-1023.
Huh7 cells
10 μM
12 h
XMU-MP-1 significantly reduced HAMP expression in Huh7 cells, even in the presence of BMP6.
Research (Wash D C). 2023 Nov 30;6:0281.
Primary hepatocytes
10 μM
XMU-MP-1 significantly reduced Hamp expression in primary hepatocytes from both Tmprss6-LKO mice and control littermates.
Research (Wash D C). 2023 Nov 30;6:0281.
C3H10T1/2 cells
10 μM
24 h
XMU-MP-1 increased the expression of Col2α1 and Col9α2.
Nat Commun. 2020 Jan 15;11(1):282.
XMU-MP-1 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice
Achilles tendon punch injury model
Intraperitoneal
2 mg/kg
Three times a week for 3 weeks
XMU-MP-1 suppressed ectopic bone formation
Nat Commun. 2025 Jan 16;16(1):749
Mice
DBA/1 mouse model
Intraperitoneal injection
2 mg/kg
Three times a week for 16 weeks
To investigate the effect of XMU-MP-1 on new bone formation in DBA/1 mouse model, results showed that XMU-MP-1 significantly reduced new bone formation.
Ann Rheum Dis. 2021 Jul;80(7):891-902
Nude mice
NSCLC xenograft model
Intraperitoneal injection
1 mg/kg
Twice a week for three weeks
XMU-MP-1 partially counteracted the inhibitory effect of ACADL on NSCLC cell growth.
Cancer Cell Int. 2024 Feb 24;24(1):86.
Mice
LPS-induced lung injury model
Intraperitoneal injection
2 mg/kg
Single injection, lungs collected at 12 and 24 hours post-infection
Mice treated with XMU-MP-1 in the LPS-induced lung injury model exhibited more severe inflammatory response and tissue damage, increased proportion of CD86-positive cells in lung tissue, and elevated mRNA expression of IL-1β, IL-6, and TNF-α.
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