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- | AM 095 / BMS
Preclinical, Journal, Metastases: Integration of an LPAR1 Antagonist into Liposomes Enhances Their Internalization and Tumor Accumulation in an Animal Model of Human Metastatic Breast Cancer. (Pubmed Central) - Oct 16, 2023
Molecular dynamics simulations show that the integration of AM095 or Ki16425 modified the physical and mechanical properties of the lipid bilayer, making it more flexible in these liposomal formulations compared with liposomes without drug. The incorporation of an LPAR1 antagonist within a liposomal drug delivery system represents a viable therapeutic approach for targeting the LPA-LPAR1 axis, which may hinder the progression of MBC.
- | AM 095 / BMS
Journal: Lysophosphatidic Acid Induces Podocyte Pyroptosis in Diabetic Nephropathy by an Increase of Egr1 Expression via Downregulation of EzH2. (Pubmed Central) - Jul 2, 2023
In podocytes from STZ-induced diabetic mice, AM095 suppressed Egr1 expression increase and EzH2/H3K27me3 expression reduction. Collectively, these results demonstrate that LPA induces NLRP3 inflammasome activation by downregulating EzH2/H3K27me3 and upregulating Egr1 expression, resulting in podocyte damage and pyroptosis, which may be a potential mechanism of DN progression.
- | AM 095 / BMS
Preclinical, Journal: TXA2 mediates LPA1-stimulated uterine contraction in late pregnant mouse. (Pubmed Central) - Jun 12, 2023
Moreover, selective thromboxane receptor (TP) antagonist, SQ-29548, and Rho kinase inhibitor, Y-27632 almost eliminated LPA-induced uterine contractions. LPA1 stimulation elicits contractions in the late pregnant mouse uterus using the contractile prostanoid, TXA2 and may be targeted to induce labor in uterine dysfunctions/ dystocia.
- | AM 095 / BMS
Journal: Positive association between plasmatic levels of orexin A and the endocannabinoid-derived 2-arachidonoyl lysophosphatidic acid in Alzheimer's disease. (Pubmed Central) - Dec 6, 2022
Finally, by patch-clamp recording we documented that 2-AGP-mediated pT231-Tau phosphorylation impairs glutamatergic transmission in the mouse hippocampus. Although further additional research is still required to clarify the potential role of orexin signaling in neurodegeneration, this study provides evidence that counteraction of aberrant OX-A signaling, also via LPA-1R antagonism, may be beneficial in the mild-to-moderate age-related cognitive decline associated with sleep disturbances.
- AM 095 / BMS
Hypoxia is a key driver of the formation of invadosomes, an abundant structure found in fibroblast derived from patients with IPF (Silfurberg B ) - Nov 8, 2022 - Abstract #ICLAF2022ICLAF_279;
PDGF, LPA and hypoxia stimulation increased healthy fibroblasts invadosome formation by 1.9 times (p<0.01, n=5), 2.3 times (p<0.01, n=5) and 1.5 times (p<0.05, n=6) respectively. Interestingly, the addition of nintedanib (RTK inhibitor) or AM095 (LPA1 receptor antagonist) blocked hypoxia-induced invadosomes.We conclude that hypoxia may play a role in lung fibroblast invadosome formation in IPF, at least in part through pathways involving tyrosine kinase and LPA receptor signaling.
- | AM 095 / BMS
Journal: Lysophosphatidic Acid Promotes Epithelial-Mesenchymal Transition in Kidney Epithelial Cells via the LPAR1/MAPK-AKT/KLF5 Signaling Pathway in Diabetic Nephropathy. (Pubmed Central) - Oct 1, 2022
Similarly, we found that LPA decreased E-cadherin expression and increased vimentin expression in HK-2 cells, which was reversed by treatment with ki16425 or AM095 (LPAR1 inhibitor)...Inhibition of the extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and serine-threonine kinase (AKT) pathways decreased LPA-induced expression of KLF5 and EMT markers. In conclusion, these data suggest that LPA contributes to the pathogenesis of diabetic nephropathy by inducing EMT and renal tubular fibrosis via regulation of KLF5 through the LPAR1.
- | AM 095 / BMS
Journal: Lysophosphatidic acid stimulates pericyte migration via LPA receptor 1. (Pubmed Central) - Jul 9, 2022
LPAR1 expression was also detected in human pericyte culture and LPA treatment of these cells also induced migration. Taken together these findings imply that LPA-LPAR1 signaling is one of the key mechanisms modulating pericyte migration, which may help to control vascular function during development and repair processes.
- | AM 095 / BMS
Preclinical, Journal: Effects of a lysophosphatidic acid receptor 1 antagonist on hypertensive renal injury in Dahl-Iwai salt-sensitive rats. (Pubmed Central) - Jun 22, 2022
Furthermore, combined administration of AM095 with an angiotensin-converting enzyme (ACE) inhibitor reduced the levels of proximal tubular injury markers and kidney weight increase, and suppressed renal fibrosis more effectively than administration of either agent alone, independent of the antihypertensive effect of the ACE inhibitor. These results provide the first evidence of the potential efficacy of LPA antagonist in suppressing renal injury in hypertensive DS rats, suggesting the promise of LPA antagonists as a novel therapeutic option for hypertensive renal injury.
- | AM 095 / BMS
Journal: The ATX-LPA Axis Regulates Vascular Permeability during Cerebral Ischemic-Reperfusion. (Pubmed Central) - Apr 30, 2022
LPA receptor inhibitors Ki16425 and AM095 attenuated the LPA-induced changes in the endothelial permeability and junctional proteins...The upregulation of ATX with hypoxic reperfusion leads to LPA production in brain endothelial cells favoring permeability. Inhibition of the ATX-LPA-LPAR axis could be therapeutically targeted in stroke to achieve better outcomes.
- | AM 095 / BMS
Journal: Glucagon-like Peptide-1 Secretion Is Inhibited by Lysophosphatidic Acid. (Pubmed Central) - Apr 30, 2022
In agreement, inhibition of GLP-1 secretion was reversed by the LPAR1/3 antagonist Ki16425, the LPAR1 antagonists AM095 and AM966, or the LPAR2 antagonist LPA2-antagonist 1...GLUTag L-cell and mouse serum DPP4 activity was unchanged by LPA or LPAR antagonists. LPA therefore impairs GLP-1 secretion in vitro and in vivo through Gα-coupled LPAR1/3 signaling, providing a new mechanism linking inflammation with impaired GSIS.
- | AM 095 / BMS
Journal: LPA signaling drives Schwann cell dedifferentiation in experimental autoimmune neuritis. (Pubmed Central) - Mar 23, 2022
LPA therefore impairs GLP-1 secretion in vitro and in vivo through Gα-coupled LPAR1/3 signaling, providing a new mechanism linking inflammation with impaired GSIS. Thus, LPA signaling may present a novel therapeutic target for the treatment of inflammatory neuropathies, potentially affecting regenerative responses in the peripheral nerve by modulating Schwann cell differentiation.
- | AM 095 / BMS
Preclinical, Journal: Interfering with lysophosphatidic acid receptor edg2/lpa signalling slows down disease progression in SOD1-G93A transgenic mice. (Pubmed Central) - Mar 5, 2022
Consequently, disrupting lpa slows down disease progression. This highlights LPA signalling as a potential target and/or biomarker in ALS.
- AM 095 / BMS
[VIRTUAL] Protective effect of AM095, a lysophosphatidic acid receptor 1 antagonist, on renal aging (Room 4) - Aug 20, 2021 - Abstract #KSN2021KSN_334;
- LPA pathway modulators (AM-966) / , AM 095 / BMS
[VIRTUAL] LPA1 signal transduction drives Schwann cell dedifferentiation in experimental autoimmune neuritis () - Nov 28, 2020 - Abstract #DGN2020DGN_322;
The myelin thickness was not affected by AM095 treatment. These results suggest that disruption of LPA1 signal transduction may represent a new therapeutic target for the treatment of inflammatory neuropathies that may modulate the regenerative responses in the peripheral nerve Schwann cell differentiation.
- | LPA pathway modulators (AM-966) / , AM 095 / BMS
Journal: Inhibition of LPA Signaling Impedes Conversion of Human Tenon's Fibroblasts into Myofibroblasts Via Suppressing TGF-β/Smad2/3 Signaling. (Pubmed Central) - Jun 19, 2020
By using an LPA-specific inhibitor, AM095, we confirmed that LPA signaling but not LPA or LPA is involved in TGF-β1 induced HTFs activation. Our results show that inhibition of LPA signaling presents potent antifibrotic effect in HTFs, which may serve as a promising intervention strategy for preventing subconjunctival fibrosis caused by glaucoma filtration surgery.
- | LPA pathway modulators (AM-966) / , AM 095 / BMS
Journal: Lysophosphatidic acid receptor 1 (LPA) plays critical roles in microglial activation and brain damage after transient focal cerebral ischemia. (Pubmed Central) - Feb 14, 2020
Our results show that inhibition of LPA signaling presents potent antifibrotic effect in HTFs, which may serve as a promising intervention strategy for preventing subconjunctival fibrosis caused by glaucoma filtration surgery. This study demonstrates that LPA is a new etiological factor for cerebral ischemia, strongly indicating that its modulation can be a potential strategy to reduce ischemic brain damage.
- | LPA pathway modulators (AM-966) / , AM 095 / BMS
Preclinical, Journal, IO Biomarker: Lysophosphatidic acid receptor 1 inhibitor, AM095, attenuates diabetic nephropathy in mice by downregulation of TLR4/NF-κB signaling and NADPH oxidase. (Pubmed Central) - Feb 7, 2020
Pharmacological or siRNA inhibition of TLR4 and NADPH oxidase mimicked the effects of AM095 in vitro. In conclusion, AM095 is effective in preventing the pathogenesis of DN by inhibiting TLR4/NF-κB and the NADPH oxidase system, consequently inhibiting the inflammatory signaling cascade in renal tissue of diabetic mice, suggesting that LPAR1 antagonism might provide a potential therapeutic target for DN.
- |||| LPA pathway modulators (AM-966) / , AM 095 / BMS
Checkpoint inhibition: Simultaneously, @NCItreatment also developed CITN12, as noted earlier, and AMC095. But we didn’t wait for those results to push for inclusion on our other immune checkpoint inhibitor trials. (Twitter) - Dec 1, 2019
- | LPA pathway modulators (AM-966) / , PF-8380 / Pfizer, AM 095 / BMS
Journal: Pharmacologic targeting of the ATX/LPA axis attenuates bleomycin-induced pulmonary fibrosis. (Pubmed Central) - Mar 29, 2019
In this report, we examined head-to-head the efficacy of a potent inhibitor of ATX (PF-8380), that has not been tested in pulmonary fibrosis models, and an antagonist of LPAR1 (AM095) in bleomycin (BLM)-induced pulmonary fibrosis. Both compounds abrogated the development of pulmonary fibrosis and prevented the distortion of lung architecture, exhibiting qualitative and quantitative differences in different manifestations of the modeled disease.