AM966LPA1 antagonist, oral active, high affinity, selective, CAS# 1228690-19-4 |
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Quality Control & MSDS
Number of papers citing our products
Chemical structure
3D structure
| Cas No. | 1228690-19-4 | SDF | Download SDF |
| PubChem ID | 46240292 | Appearance | Powder |
| Formula | C27H23ClN2O5 | M.Wt | 490.93 |
| Type of Compound | N/A | Storage | Desiccate at -20°C |
| Solubility | DMSO : 100 mg/mL (203.70 mM; Need ultrasonic) | ||
| Chemical Name | 2-[4-[4-[4-[[(1R)-1-(2-chlorophenyl)ethoxy]carbonylamino]-3-methyl-1,2-oxazol-5-yl]phenyl]phenyl]acetic acid | ||
| SMILES | CC1=NOC(=C1NC(=O)OC(C)C2=CC=CC=C2Cl)C3=CC=C(C=C3)C4=CC=C(C=C4)CC(=O)O | ||
| Standard InChIKey | WWQTWEWAPUCDDZ-QGZVFWFLSA-N | ||
| Standard InChI | InChI=1S/C27H23ClN2O5/c1-16-25(29-27(33)34-17(2)22-5-3-4-6-23(22)28)26(35-30-16)21-13-11-20(12-14-21)19-9-7-18(8-10-19)15-24(31)32/h3-14,17H,15H2,1-2H3,(H,29,33)(H,31,32)/t17-/m1/s1 | ||
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months. Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it. |
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| About Packaging | 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial. 2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial. 3. Try to avoid loss or contamination during the experiment. |
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| Shipping Condition | Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request. | ||
| 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 | |||||
| Cell experiment: [1] | |
| Cell lines | CHO cells (stably expressing human LPA1 or mouse LPA1) |
| 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. |
| Reacting condition | 100 nM, 30 min for 100% calcium release inhibition 469 nM, 15 min for chemotaxis inhibition (IC50) |
| 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] | |
| Animal models | Female C57BL/6 mice |
| Dosage form | Oral administration, 30 or 60 mg/kg, twice daily |
| Application | 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. |
| 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. |
| 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. | |
AM966 Dilution Calculator
AM966 Molarity Calculator
| 1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
| 1 mM | 2.037 mL | 10.1848 mL | 20.3695 mL | 40.739 mL | 50.9238 mL |
| 5 mM | 0.4074 mL | 2.037 mL | 4.0739 mL | 8.1478 mL | 10.1848 mL |
| 10 mM | 0.2037 mL | 1.0185 mL | 2.037 mL | 4.0739 mL | 5.0924 mL |
| 50 mM | 0.0407 mL | 0.2037 mL | 0.4074 mL | 0.8148 mL | 1.0185 mL |
| 100 mM | 0.0204 mL | 0.1018 mL | 0.2037 mL | 0.4074 mL | 0.5092 mL |
| * Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations. | |||||
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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].
References:
[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.
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AM966, an Antagonist of Lysophosphatidic Acid Receptor 1, Increases Lung Microvascular Endothelial Permeability through Activation of Rho Signaling Pathway and Phosphorylation of VE-Cadherin.[Pubmed:28348461]
Mediators Inflamm. 2017;2017:6893560.
Maintenance of pulmonary endothelial barrier integrity is important for reducing severity of lung injury. Lysophosphatidic acid (LPA) regulates cell motility, cytoskeletal rearrangement, and cell growth. Knockdown of LPA receptor 1 (LPA1) has been shown to mitigate lung injury and pulmonary fibrosis. AM966, an LPA1 antagonist exhibiting an antifibrotic property, has been considered to be a future antifibrotic medicine. Here, we report an unexpected effect of AM966, which increases lung endothelial barrier permeability. An electric cell-substrate sensing (ECIS) system was used to measure permeability in human lung microvascular endothelial cells (HLMVECs). AM966 decreased the transendothelial electrical resistance (TEER) value immediately in a dose-dependent manner. VE-cadherin and f-actin double immunostaining reveals that AM966 increases stress fibers and gap formation between endothelial cells. AM966 induced phosphorylation of myosin light chain (MLC) through activation of RhoA/Rho kinase pathway. Unlike LPA treatment, AM966 had no effect on phosphorylation of extracellular signal-regulated kinases (Erk). Further, in LPA1 silencing cells, we observed that AM966-increased lung endothelial permeability as well as phosphorylation of VE-cadherin and focal adhesion kinase (FAK) were attenuated. This study reveals that AM966 induces lung endothelial barrier dysfunction, which is regulated by LPA1-mediated activation of RhoA/MLC and phosphorylation of VE-cadherin.
