AM095 suppresses the LPA-triggered calcium movement in CHO cells that are genetically modified to express either human or mouse LPA1. The IC50 values for the suppression of LPA-evoked calcium movement by AM095 in CHO cells expressing human or mouse LPA1 are 0.025 μM and 0.023 μM, respectively[1]. AM095 diminishes the LPA-induced vasorelaxation by approximately 90% at a concentration of 10 μM compared to the control treated with a vehicle[2]. AM095 hinders the LPA-driven chemotaxis of CHO cells that overexpress mouse LPA1 (IC50=778 nM) and human A2058 melanoma cells (IC50=233 nM)[3].
体内研究
AM095 exhibits notable oral bioavailability and a moderate half-life, showing tolerability in rats and dogs following oral and intravenous administration. AM095 progressively inhibits the LPA-induced release of histamine. It also reduces the bleomycin-triggered rise in collagen, protein, and the infiltration of inflammatory cells in bronchoalveolar lavage fluid. Additionally, AM095 lessens kidney fibrosis in a model of unilateral ureteral obstruction in mice[3].
体外研究
AM095 suppresses the LPA-triggered calcium movement in CHO cells that are genetically modified to express either human or mouse LPA1. The IC50 values for the suppression of LPA-evoked calcium movement by AM095 in CHO cells expressing human or mouse LPA1 are 0.025 μM and 0.023 μM, respectively[1].
AM095 diminishes the LPA-induced vasorelaxation by approximately 90% at a concentration of 10 μM compared to the control treated with a vehicle[2].
AM095 hinders the LPA-driven chemotaxis of CHO cells that overexpress mouse LPA1 (IC50=778 nM) and human A2058 melanoma cells (IC50=233 nM)[3].
AM095 free acid 细胞实验
Cell Line
Concentration
Treated Time
Description
References
CHO cells
0.98 μM, 0.73 μM
Inhibited LPA-induced calcium flux
Mol Pharm. 2023 Nov 6;20(11):5500-5514.
Human brain microvascular endothelial cells (HBMEC)
10 μM
LPA increased permeability in HBMEC.
Int J Mol Sci. 2022 Apr 8;23(8):4138.
E11 cells
10 µm
4.5 h
Assess pyroptosis. LPA significantly increased the number of pyroptotic cells, while AM095 significantly suppressed this increase.
Int J Mol Sci. 2023 Jun 9;24(12):9968.
E11 cells
10 µM
3 or 6 h
Measure protein levels of NEK7, NLRP3, ASC, cleaved-caspase-1, N-GSDMD, and IL-1β. LPA significantly increased the expression of these factors, while AM095 significantly suppressed LPA-induced expression.
Int J Mol Sci. 2023 Jun 9;24(12):9968.
mouse primary microglia
2 μM
24 h
Suppressing LPA1 activity reduced mRNA expression levels of proinflammatory cytokines (TNF-α, IL-6, IL-1β) in LPS-stimulated microglia
AM095 significantly attenuated the LPA-induced changes in endothelial permeability and junctional proteins.
Int J Mol Sci. 2022 Apr 8;23(8):4138.
GLUTag L-cells
2.5 μM
2.5 h
To test whether LPA inhibits GLP-1 secretion through LPAR1/3 signaling. Results showed LPA significantly inhibited GLP-1 secretion, and this inhibition was reversed by the LPAR1/3 antagonist Ki16425
Int J Mol Sci. 2022 Apr 9;23(8):4163.
HK-2 cells
10 μM
48 h
AM095 inhibits LPA-induced expression of EMT markers and fibrotic factors
Int J Mol Sci. 2022 Sep 10;23(18):10497.
primary hippocampal neurons
300 nM
45 min
OX-A induces 2-AG biosynthesis via OX-1R, which is then converted to 2-AGP, leading to increased pT231-Tau phosphorylation
Front Aging Neurosci. 2022 Nov 16;14:1004002.
AM095 free acid 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
C57BL/6J mice
STZ-induced diabetic mice
Oral
30 mg/kg
Once daily for 8 weeks
Evaluate the effect of AM095 on podocyte loss and death in the kidneys of STZ-induced diabetic mice. AM095 significantly inhibited podocyte loss and death.
Int J Mol Sci. 2023 Jun 9;24(12):9968.
ICR mice
Transient middle cerebral artery occlusion (tMCAO) model
Oral gavage
30 mg/kg
Single dose immediately after reperfusion, assessed at 1 or 3 days post-tMCAO
AM095 significantly attenuated tMCAO-induced brain infarction and neurological deficits, and suppressed microglial activation, proliferation, and proinflammatory responses
J Neuroinflammation. 2019 Aug 20;16(1):170.
Lewis rats
Experimental autoimmune neuritis (EAN)
Oral gavage
10 mg/kg
Once daily from 10 to 28 days post-immunization
To evaluate the effect of AM095 on clinical scores and remyelination in EAN. Results showed significant improvement in clinical scores, particularly during the remission phase, and an increase in the number of large-caliber myelinated axons.
J Neuroinflammation. 2021 Dec 17;18(1):293
C57BL/6J mice
Ischemia-reperfusion model
Intraperitoneal injection
30 mg/kg
Single dose
The ATX inhibitor PF8380 significantly attenuated ATX activity and permeability in mouse brains.
Int J Mol Sci. 2022 Apr 8;23(8):4138.
Mice
C57Bl/6J male mice
Intraperitoneal injection
50 mg/kg
Single injection, measured after 30 minutes
To test whether LPA inhibits GLP-1 secretion in vivo. Results showed LPA caused an ~50% fall in circulating GLP-1, and this effect was prevented by LPAR1/3 antagonist Ki16425
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