AM966
AM966 is a selective, potent and orally bioavailable antagonist of lysophosphatidic acid type 1 receptor (LPA1) with IC50 values of 17 and 19 nM for human or mouse LPA1, respectively [1]. Relative to LPA2, 3, 4, 5 receptors, AM966 shows 10-fold and 100-fold more selective in mouse and human cell lines for LPA1, respectively [1].
In vitro, AM966 shows to inhibit LPA-induced chemotaxis in IMR-90 human lung fibroblasts, A2058 human melanoma cells and CHO cells expressing LPA1 receptors [1].
In vivo, AM966 has been demonstrated to reduce total BALF cells, LDH activity, BALF collagen and total TGFβ concentrations in bleomycin-induced mice. Moreover, AM966 has been reported to block lung fibrosis, reduce lung inflammation and maintain body weight in mice induced by bleomycin [1].
Reference:
[1] Swaney JS1, Chapman C, Correa LD, Stebbins KJ, Bundey RA, Prodanovich PC, Fagan P, Baccei CS, Santini AM, Hutchinson JH, Seiders TJ,Parr TA, Prasit P, Evans JF, Lorrain DS. A novel, orally active LPA(1) receptor antagonist inhibits lung fibrosis in the mouse bleomycin model. Br J Pharmacol. 2010 Aug;160(7):1699-713.
- 1. Li M, Lv Y, et al. "Co-stimulation of LPAR(1) and S1PR(1/3) increases the transplantation efficacy of human mesenchymal stem cells in drug-induced and alcoholic liver diseases." Stem Cell Res Ther. 2018 Jun 14;9(1):161. PMID:29898789
- 2. Cai J, Wei J, et al."AM966, an Antagonist of Lysophosphatidic Acid Receptor 1, Increases Lung Microvascular Endothelial Permeability through Activation of Rho Signaling Pathway and Phosphorylation of VE-Cadherin. Mediators Inflamm."2017;2017:6893560. PMID:28348461
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 490.93 |
| Cas No. | 1228690-19-4 |
| Formula | C27H23ClN2O5 |
| Synonyms | AM 966;AM-966 |
| Solubility | ≥24.55 mg/mL in DMSO; insoluble in H2O; ≥2.24 mg/mL in EtOH with gentle warming and ultrasonic |
| Chemical Name | 2-[4-[4-[4-[[(1R)-1-(2-chlorophenyl)ethoxy]carbonylamino]-3-methyl-1,2-oxazol-5-yl]phenyl]phenyl]acetic acid |
| SDF | Download SDF |
| Canonical SMILES | CC1=NOC(=C1NC(=O)OC(C)C2=CC=CC=C2Cl)C3=CC=C(C=C3)C4=CC=C(C=C4)CC(=O)O |
| 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 |
CHO cells (stably expressing human LPA1 or mouse LPA1) |
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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 |
100 nM, 30 min for 100% calcium release inhibition 469 nM, 15 min for chemotaxis inhibition (IC50) |
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Applications |
CHO cells were pre-treated with increasing concentrations of AM966 for 30 min and then stimulated with LPA (10–30 nM) and calcium release was measured. AM966 inhibited LPA-stimulated intracellular calcium release from CHO cells stably expressing human and mouse LPA1 receptors. AM966 was also evaluated for inhibition of LPA-induced chemotaxis in CHO cells stably expressing mouse LPA1 receptors. The IC50 value was 469±54 nM. |
| Animal experiment: [1] | |
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Animal models |
Female C57BL/6 mice |
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Dosage form |
Oral administration, 30 or 60 mg/kg, twice daily |
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Applications |
No reduction in lung fibrosis was observed in response to low dose AM966 (10 mg·kg-1). However, AM966 at 30 and 60 mg·kg-1 dramatically reduced lung tissue remodelling and fibrosis so that lung architecture in these groups was similar to that of the vehicle group. |
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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] Swaney J S, Chapman C, Correa L D, et al. A novel, orally active LPA1 receptor antagonist inhibits lung fibrosis in the mouse bleomycin model. British journal of pharmacology, 2010, 160(7): 1699-1713. |
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| Description | AM966 is a high affinity, selective, oral antagonist of LPA1 receptor (lysophosphatidic acid receptor) with an IC50 value of 17 nM. | |||||
| Targets | LPA1 receptor | |||||
| IC50 | 17 nM | |||||
Quality Control & MSDS
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Chemical structure
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Related Biological Data
