1. GPCR/G Protein
  2. LPL Receptor

AM966 

Cat. No.: HY-15277 Purity: 98.75%
Handling Instructions

AM966 is a high affinity, selective, oral LPA1-antagonist, inhibits LPA-stimulated intracellular calcium release (IC50=17 nM).

For research use only. We do not sell to patients.

AM966 Chemical Structure

AM966 Chemical Structure

CAS No. : 1228690-19-4

Size Price Stock Quantity
Free Sample (0.5-1 mg)   Apply now  
10 mM * 1 mL in DMSO USD 238 In-stock
Stock in the United States
Estimated Time of Arrival: December 31
5 mg USD 216 In-stock
Stock in Sweden
Estimated Time of Arrival: December 31
10 mg USD 372 In-stock
Stock in Sweden
Estimated Time of Arrival: December 31
50 mg USD 1080 In-stock
Stock in the United States
Estimated Time of Arrival: December 31
100 mg USD 1320 In-stock
Stock in the United States
Estimated Time of Arrival: December 31
200 mg   Get quote  
500 mg   Get quote  

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    AM966 purchased from MCE. Usage Cited in: J Pharmacol Exp Ther. 2016 Nov;359(2):340-353.

    Concentration-dependent effects of LPA receptor antagonists on antidepressant- and LPA-induced ERK1/2 phosphorylation in C6 glioma cells. Cells are pre-incubated with either vehicle or the indicated concentrations of AM966 for 10 min and then exposed to either vehicle or 1 μM LPA (A), 15 μM Amitriptyline (C) or 5 μM Mianserin (E) for 10 min.

    AM966 purchased from MCE. Usage Cited in: Biochem Pharmacol. 2015 Jun 15;95(4):311-23.

    CHO-K1 cells express LPA1 receptors coupled to ERK1/2 phosphorylation. Inhibition of LPA-induced phospho-ERK1/2 by AM966. Cells are pre-incubated with either vehicle or the indicated concentrations of AM966 for 30 min and then treated with LPA (300 nM) for 15 min. Values are expressed as percent of p-ERK stimulation elicited by LPA in the absence of antagonist and are the mean ± SEM of three experiments.

    AM966 purchased from MCE. Usage Cited in: J Biol Chem. 2016 Dec 30;291(53):27364-27370.

    Effect of LPAR antagonists on ERK1/2 phosphorylation and FRS2 phosphorylation evoked by either amitriptyline (A) or LPA (B).

    AM966 purchased from MCE. Usage Cited in: WASHINGTON STATE UNIVERSITY. MAY 2015.

    Effects of LPAR antagonists on growth factor-induced phosphorylation of ERK in DU145 cells. Serum starved DU145 cells are incubated with 10 μM LPA, with or without either 100 nM AM966 or 10 μM Ki16425 for 10 minutes. Whole-cell extracts, equalized for protein, are immunoblotted for phospho-ERK (pERK) and for actin (loading control).
    • Biological Activity

    • Protocol

    • Technical Information

    • Purity & Documentation

    • References

    Description

    AM966 is a high affinity, selective, oral LPA1-antagonist, inhibits LPA-stimulated intracellular calcium release (IC50=17 nM).

    IC50 & Target

    LPA1[1]

    In Vitro

    AM966 is a potent, selective, orally bioavailable LPA1 receptor antagonist. AM966 inhibits LPA1-mediated chemotaxis of human A2058 melanoma cells (IC50=138±43 nM), IMR-90 human lung fibroblasts (IC50=182±86 nM) and CHO mLPA1 cells (IC50=469±54 nM)[1]. LPA-induced ERK1/2 activation is completely blocked by AM966 (100 nM), which selectively antagonizes LPA1 over LPA2-5, with an IC50 value of 3.8±0.4 nM. Pre-treatment with AM966 (100 nM) completely blocks ERK1/2 phosphorylation induced by either amitriptyline or mianserin[2].

    In Vivo

    AM966 (30 mg/kg, BID) reduces vascular leakage, inflammation and lung injury and inflammation in a 3 day bleomycin model. AM966 inhibits lung fibrosis, maintains mouse body weight and decreases lung inflammation 14 days after bleomycin lung injury. AM966 reduces vascular leakage, tissue injury and pro-fibrotic cytokine production in the 14 day bleomycin study. AM966 demonstrates greater efficacy compared to pirfenidone in the 14 day bleomycin model. AM966 decreases mortality and fibrosis at late time points after bleomycin injury[1].

    References
    Preparing Stock Solutions
    Concentration Volume Mass 1 mg 5 mg 10 mg
    1 mM 2.0370 mL 10.1848 mL 20.3695 mL
    5 mM 0.4074 mL 2.0370 mL 4.0739 mL
    10 mM 0.2037 mL 1.0185 mL 2.0370 mL
    Please refer to the solubility information to select the appropriate solvent.
    Cell Assay
    [2]

    AM966 (Chem Scene, Monmouth Junction, NJ, USA) is dissolved in DMSO and stored, and then diluted with appropriate media (DMSO 0.5%) before use[2].

    CHO-K1 cells are grown to 80% confluency in 12-well plates, serum-starved for 24 h and incubated in serum-free medium with AM966. After 21 h, [3H]thymidine (0.5 μCi/well) is added and the incubation is continued for 3 h. The medium is then removed, and the cells are placed on ice and washed twice with 1 mL of ice-cold PBS containing 5% trichloroacetic acid. Cells are solubilized and [3H]thymidine incorporation is determined by liquid scintillation counting. Assays are performed in triplicate[2]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Animal Administration
    [1]

    AM966 is prepared in water (Mice)[1].

    Mice[1]
    The oral exposure of AM966 is determined in fasted mice. Animals received AM966 (10 mg/kg) in vehicle (water) by oral gavage and are then killed by CO2 inhalation at 1, 2, 4, 8 and 24 h post dose (n=2 animals per time point for each test compound). Blood (approximately 300 µL) is collected via cardiac puncture into EDTA-containing tubes and centrifuged at 1450×g for 10 min. The plasma is removed and analysed for AM966 content by liquid chromatography-mass spectrometry (LCMS). Briefly, known amounts of AM966 are added to thawed mouse plasma to yield a concentration range from 0.8 to 4000 ng/mL. Mouse plasma samples are precipitated using acetonitrile (1:4, v:v) containing the internal standard buspirone. A 10 µL aliquot of the analyte mixture is injected using a Leap PAL autosampler. Analyses are performed using an Agilent Zorbax SB-C8 column (2.1×50 mm; 5 µm) linked to a Shimadzu LC-10AD VP with SCL-10A VP system controller. Tandem mass spectrometric detection is carried out on a PE Sciex API3200 in the positive ion mode (ESI) by multiple reaction monitoring. The calibration curves are constructed by plotting the peak-area ratio of analysed peaks against known concentrations. The lower limit of quantitation is 0.8 ng/mL. The data are subjected to linear regression analysis with 1/x2weighting. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    References
    Molecular Weight

    490.93

    Formula

    C₂₇H₂₃ClN₂O₅

    CAS No.

    1228690-19-4

    SMILES

    O=C(O)CC1=CC=C(C2=CC=C(C3=C(NC(O[[email protected]@H](C4=CC=CC=C4Cl)C)=O)C(C)=NO3)C=C2)C=C1

    Storage
    Powder -20°C 3 years
      4°C 2 years
    In solvent -80°C 6 months
      -20°C 1 month
    Shipping

    Room temperature in continental US; may vary elsewhere

    Solvent & Solubility

    DMSO: ≥ 105 mg/mL

    * "<1 mg/mL" means slightly soluble or insoluble. "≥" means soluble, but saturation unknown.

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    Product Name:
    AM966
    Cat. No.:
    HY-15277
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