AM095
AM095 is a novel, potent and orally bioavailable antagonist of lysophosphatidic acid type 1 receptor (LPA1) with IC50 values of 0.73 and 0.98 μM for mouse or recombinant human LPA1, respectively [1].
In vitro, AM095 has shown to inhibit LPA1-induced chemotaxis of both mouse LPA1/CHO cells and human A2058 melanoma cells with IC50 values of 0.78 μM and 0.23μM [1].
In vivo, AM095 could dose-dependently block LPA-induced histamine release with an ED50 value of 8.3 mg/kg in mice. Additionally, AM095 has been revealed to remarkably reduce the BALF collagen and protein with an ED50 value of 10 mg/kg in lungs. AM095 has also shown to decrease both macrophage and lymphocyte infiltration induced by bleomycin in mice [1].
References:
[1] Swaney JS1, Chapman C, Correa LD, Stebbins KJ, Broadhead AR, Bain G, Santini AM, Darlington J, King CD, Baccei CS, Lee C, Parr TA, Roppe JR, Seiders TJ, Ziff J, Prasit P, Hutchinson JH, Evans JF, Lorrain DS. Pharmacokinetic and pharmacodynamic characterization of an oral lysophosphatidic acid type 1 receptor-selective antagonist. J Pharmacol Exp Ther. 2011 Mar;336(3):693-700.
- 1. Xiang Zhang, Harry Cheuk-Hay Lau, et al. "Intestinal TM6SF2 protects against metabolic dysfunction-associated steatohepatitis through the gut–liver axis." Nat Metab. 2025 Jan;7(1):102-119 PMID: 39779889
- 2. Mégane Lebel, Dominic O Cliche, et al. "Hypoxia Promotes Invadosome Formation by Lung Fibroblasts." Cells. 2024 Jul 6;13(13):1152. PMID: 38995003
- 3. Ingrid Lua, Steven Balog, et al. "Loss of lysophosphatidic acid receptor 1 in hepatocytes reduces steatosis via down-regulation of CD36." Prostaglandins Other Lipid Mediat. 2021 Oct;156:106577. PMID:34147666
- 4. Harper K, R Lavoie R, et al. "The Hypoxic Tumor Microenvironment Promotes Invadopodia Formation and Metastasis through LPA1 Receptor and EGFR Cooperation." Mol Cancer Res. 2018 Jun 4. pii:molcanres.0649.2017. PMID:29866927
- 5. Szepanowski F, Szepanowski LP, et al. "Lysophosphatidic acid propagates post-injury Schwann cell dedifferentiation through LPA(1) signaling. Neurosci Lett." 2017 Oct 16;662:136-141. PMID:29051083
- 6. Banks DB, Chan GN, et al. "Lysophosphatidic acid and amitriptyline signal through LPA1R to reduce P-glycoprotein transport at the blood-brain barrier." J Cereb Blood Flow Metab. 2018 May;38(5):857-868. PMID:28447863
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 478.47 |
| Cas No. | 1345614-59-6 |
| Formula | C27H23N2NaO5 |
| Synonyms | AM 095;AM-095 |
| Solubility | ≥23.9 mg/mL in DMSO; insoluble in H2O; ≥16.77 mg/mL in EtOH with ultrasonic |
| Chemical Name | sodium;2-[4-[4-[3-methyl-4-[[(1R)-1-phenylethoxy]carbonylamino]-1,2-oxazol-5-yl]phenyl]phenyl]acetate |
| SDF | Download SDF |
| Canonical SMILES | CC1=NOC(=C1NC(=O)OC(C)C2=CC=CC=C2)C3=CC=C(C=C3)C4=CC=C(C=C4)CC(=O)[O-].[Na+] |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Cell experiment: [1] | |
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Cell lines |
MDA-MB-231 cells and SK-OV3 cells |
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Preparation method |
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months. |
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Reaction Conditions |
500 nM, 5 min |
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Applications |
Cells were pretreated with AM-095 or vehicle for 5 min and then treated with 10 μM of LPE or LPA. AM-095 (500 nM) completely inhibited LPA-induced [Ca2+]i responses in both cell lines and LPE-induced [Ca2+]i responses in MDA-MB-231 cells. AM-095 (500 nM) did not affect LPE-induced [Ca2+] i responses in SK-OV3 cells. |
| Animal experiment : [2] | |
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Animal models |
Female CD-1 mice |
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Dosage form |
Oral administration, 1–30 mg/kg |
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Applications |
Mice received AM095 in a volume of 10 ml/kg 2 h before the intravenous LPA (300 μg/mouse) challenge. LPA stimulated histamine release in a dose-dependent manner, resulting in a nearly 14-fold stimulation at the highest concentration tested. AM095 dose-dependently inhibited histamine release with an ED50 of 8.3 mg/kg and a maximal reduction of 80% at a dose of 30 mg/kg. By plotting the percentage inhibition of histamine release versus AM095 plasma concentrations for each individual animal and assuming a maximum response of 80% we generated an EC50 of ~ 1.5 μM. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1] Park S J, Lee K P, Im D S. Action and Signaling of Lysophosphatidylethanolamine in MDA-MB-231 Breast Cancer Cells. Biomolecules & therapeutics, 2014, 22(2): 129. [2] Swaney J S, Chapman C, Correa L D, et al. Pharmacokinetic and pharmacodynamic characterization of an oral lysophosphatidic acid type 1 receptor-selective antagonist. Journal of Pharmacology and Experimental Therapeutics, 2011, 336(3): 693-700. |
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| Description | AM095 is a potent antagonist of LPA1 receptor with IC50 values of 0.98 and 0.73 μM for recombinant human and mouse LPA1, respectively. | |||||
| Targets | LPA1 receptor | |||||
| IC50 | 0.98 μM (recombinant human) 0.73 μM (recombinant mouse) | |||||
Quality Control & MSDS
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