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Chemical Structure| 1228690-19-4 Chemical Structure| 1228690-19-4

Structure of AM966
CAS No.: 1228690-19-4

Chemical Structure| 1228690-19-4

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AM966 is a high-affinity, selective, oral LPA1 antagonist, inhibiting LPA-stimulated intracellular calcium release with an IC50 of 17 nM.

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Product Details of AM966

CAS No. :1228690-19-4
Formula : C27H23ClN2O5
M.W : 490.93
SMILES Code : O=C(O)CC1=CC=C(C2=CC=C(C3=C(NC(O[C@@H](C4=CC=CC=C4Cl)C)=O)C(C)=NO3)C=C2)C=C1
MDL No. :MFCD20486575
InChI Key :WWQTWEWAPUCDDZ-QGZVFWFLSA-N
Pubchem ID :46240292

Safety of AM966

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Related Pathways of AM966

GPCR

Isoform Comparison

Biological Activity

In Vitro:

Cell Line
Concentration Treated Time Description References
Human lung microvascular endothelial cells (HLMVECs) 0.1, 1.0, 10.0 µM 15 minutes to 2 hours To investigate the effect of AM966 on the barrier function of HLMVECs. Results showed that AM966 rapidly decreased transendothelial electrical resistance (TEER), increased gap formation, and disrupted barrier integrity through activation of RhoA/Rho kinase pathway and phosphorylation of VE-cadherin. Mediators Inflamm. 2017;2017:6893560.
M2 macrophages 100 nM 24 hours Inhibited invasion and proliferation of JEG3 cells Autophagy. 2022 Oct;18(10):2459-2480.
IMR-90 human lung fibroblasts 181 nM (IC50) 16-18 hours To evaluate the inhibitory effect of AM966 on LPA-induced chemotaxis, results showed that AM966 effectively inhibited the chemotaxis of IMR-90 cells. Br J Pharmacol. 2010 Aug;160(7):1699-713.
CHO cells stably expressing human LPA1 receptors 17 nM (IC50) 30 minutes To evaluate the antagonistic effect of AM966 on human LPA1 receptors, results showed that AM966 effectively inhibited LPA-stimulated intracellular calcium release. Br J Pharmacol. 2010 Aug;160(7):1699-713.
A549 human non-small cell lung cancer cells 1 µM 90 minutes Blockade of LPA1 receptor, inhibiting PA-stimulated lung cancer cell migration Biomedicines. 2023 Jun 23;11(7):1804.

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Female C57BL/6 mice Bleomycin-induced lung fibrosis model Oral gavage 10, 30, 60 mg/kg Twice daily, for 3-28 days To evaluate the efficacy of AM966 in the bleomycin-induced lung fibrosis model, results showed that AM966 reduced lung injury, vascular leakage, inflammation and fibrosis, and decreased the concentrations of multiple pro-fibrotic and pro-inflammatory cytokines in BALF. Br J Pharmacol. 2010 Aug;160(7):1699-713.
CD1 mice Intracerebral hemorrhage model Oral 30 mg/kg Administered at 1 and 12 hours post-ICH AM966-mediated LPA1 suppression relieved PMN recruitment, diminished brain oedema, demonstrated extravasation (as evidenced by EBS), protected BBB integrity, and enhanced neurologic activity following ICH Fluids Barriers CNS. 2023 May 10;20(1):33
Mice C57Bl/6J male mice Intraperitoneal injection 50 mg/kg Single injection, measured after 30 minutes LPA injection caused an ~50% fall in circulating GLP-1, which was completely prevented by LPAR1/3 antagonist Ki16425, LPAR1 antagonists AM095 and AM966. LPAR2 antagonist LPA2-antagonist 1 did not significantly restore GLP-1 levels. Int J Mol Sci. 2022 Apr 9;23(8):4163.
Mice C57 /Bl6 mice Intraperitoneal injection Low dose (22 mg/kg), medium dose (33 mg/kg), and high dose (43 mg/kg) Every 24 hours for 3 days To investigate the effect of LPAR1 blockade on gastrointestinal motility and ENS structure in mice. Results showed that AM966 significantly reduced gastrointestinal transit, leading to weight loss and ENS structural alterations, including neuronal loss and glial cell morphological changes. J Clin Invest. 2022 Feb 15;132(4):e149464

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.04mL

0.41mL

0.20mL

10.18mL

2.04mL

1.02mL

20.37mL

4.07mL

2.04mL

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