WMS-1410
WMS-1410 is a selective GluN2B-containing NMDA receptor inhibitor with an IC50 of 18.4 nM. WMS-1410 regulates intracellular calcium levels and protects cells from Apoptosis. WMS-1410 inhibits glutamate-induced excitotoxicity. WMS-1410 reverses NMDA/glycine-induced reduction in glucose-stimulated insulin secretion without altering physiological insulin secretion or baseline redox status, but fails to counteract insulin content loss induced by glucolipotoxicity. WMS-1410 exhibits analgesic activity against advanced neuropathic pain. WMS-1410 can be used in studies related to stroke, brain injury, Alzheimer's disease, Parkinson's disease, type 2 diabetes, and neuropathic pain.
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- CAS No.: 1253197-38-4
- Formule: C20H25NO2
- Masse moléculaire:311.42
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Stockage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Activité biologique
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Chemical Information
- Pureté et documentation
- Références
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Activité biologique
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GluN2B 18.4 nM (IC50) |
When incubated with rat liver microsomes and NADPH/H+, WMS-1410 (300 μg; 120 min) generates four distinct phase I hydroxylated metabolites via modification of its butyl chain, phenylbutyl benzene ring, aliphatic azepine skeleton, and aromatic benzazepine ring[1].
Following incubation with rat liver microsomes and phase II conjugation cofactors, WMS-1410 (300 μg; 120 min) generates 2 direct phase II conjugation metabolites and 5 phase I/II combined metabolites via glucuronidation, sulfation and methylation reactions[1].
WMS-1410 (150 μg; 15-60 min) exhibits high metabolic stability in rat liver microsomes, with 93% of the compound remaining intact after 60 min of incubation[1].
WMS-1410 potently binds to NMDA receptors containing the GluN2B subunit, with a Ki value of 13 nM and an IC50 value of 18.4 nM for inhibiting receptor activity[1].
WMS-1410 (1 μM; 48 h) completely inhibits NMDA-induced oxidative stress in mouse islet cells after 48 hours of co-incubation[2].
WMS-1410 (0.1-1 μM; 18 h) partially attenuates NMDA/glycine-induced apoptotic death of mouse islet cells after 18 h of co-incubation[2].
WMS-1410 (1 μM; 24 h) completely blocks NMDA-induced impairment of glucose-stimulated insulin secretion in mouse islets after 24 h of co-incubation[2].
WMS-1410 (0.1-1 μM; 7 d) reduces palmitate-mediated glucolipotoxicity-induced apoptosis of mouse islet cells in a dose-dependent manner after 7 days of co-incubation[2].
WMS-1410 (1 μM) reduces the proportion of mouse islet cells that exhibit elevated intracellular calcium levels in response to acute NMDA/glycine treatment[2].
WMS-1410 (6 different concentrations; 120 min) binds to the Ifenprodil (HY-12882) binding site of L (tk−) cell membrane homogenates expressing NR1a/NR2B with a Ki value of 14 nM, exhibits excellent selectivity for σ2 receptors, and shows no significant binding to the PCP binding site of NMDA receptors[3].
WMS-1410 (1 nM-10 μM; 30 min preincubation, 4 h incubation with glutamate/glycine) inhibits glutamate/glycine-induced excitotoxicity in L13-E6 cells expressing NR1a/NR2B, with an IC50 of 18.4 nM, and exhibits only extremely low activity in cells expressing NR1a/NR2A[3].
WMS-1410 exhibits high selectivity for NR2B-containing NMDA receptors, with its selectivity surpassing that of over 100 tested receptors, transporters and enzymes, and only showing weak activity at the CGRP1 receptor and hERG channel[3].
WMS-1410 exhibits better metabolic stability than Ifenprodil in mouse and rat liver microsomes, with half-lives of 28 min and <3 min[3], respectively.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
WMS-1410 (10-100 mg/kg; i.p.; single dose) exhibits dose-dependent analgesic activity in the late neuropathic pain phase of the mouse formalin assay, with the lowest active dose being 30 mg/kg[3].
WMS-1410 (1-100 mg/kg; i.p.; single dose) is well tolerated in mice at intraperitoneal doses up to 100 mg/kg, with only mild diarrhea observed at the highest tested dose[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Wistar (female, 410 g)[1]
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Dosage:7.8 mg/kg
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Administration:i.p.; single dose
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Result:Detected parent compound in all collected urine samples.
Identified phase I metabolites 1, 2, and 3; phase II metabolites 5, 6, 7, and 8; and combined phase I/II metabolite 12.
Detected glucuronide metabolite 5 as the main in vivo metabolite.
Did not detect sulfate metabolites 9-11 (identified in vitro) in urine.
Confirmed formation of catechol phase I metabolite 4 (identified in vitro) as an in vivo intermediate via presence of downstream metabolites 7, 8, and 12.
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Animal Model:unspecified strain[3]
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Dosage:10 mg/kg; 30 mg/kg; 100 mg/kg
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Administration:i.p.; single dose
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Result:Was virtually inactive in the acute early pain phase at all tested doses.
Showed no analgesic effects at 10 mg/kg in the late neuropathic pain phase.
Exhibited dose-dependent analgesic activity starting at 30 mg/kg in the late neuropathic pain phase.
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Animal Model:unspecified strain[3]
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Dosage:1 mg/kg; 30 mg/kg; 100 mg/kg
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Administration:i.p.; single dose
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Result:Showed no unusual reactions following intraperitoneal administration at doses up to 100 mg/kg.
Caused mild diarrhea in some animals 30 minutes after injection of the 100 mg/kg dose.
Chemical Information
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CAS No. 1253197-38-4
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Masse moléculaire 311.42
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Formule C20H25NO2
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SMILES
OC1=CC=C2C(CCN(CC2O)CCCCC3=CC=CC=C3)=C1
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureté et documentation
Références
[1]. Falck E, et al. In vitro and in vivo biotransformation of WMS-1410, a potent GluN2B selective NMDA receptor antagonist. J Pharm Biomed Anal. 2014;94:36-44. [Content Brief]
[2]. Gresch A, et al. Selective Inhibition of N-Methyl-d-aspartate Receptors with GluN2B Subunit Protects β Cells against Stress-Induced Apoptotic Cell Death. J Pharmacol Exp Ther. 2021;379(3):235-244. [Content Brief]
[3]. Tewes B, et al. Conformationally constrained NR2B selective NMDA receptor antagonists derived from ifenprodil: Synthesis and biological evaluation of tetrahydro-3-benzazepine-1,7-diols. Bioorg Med Chem. 2010;18(22):8005-8015. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
WMS-1410 Related Classifications
HY-183871 Related Classifications
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- WMS-1410
- 1253197-38-4
- WMS1410
- WMS 1410
- iGluR
- Apoptosis
- Calcium Channel
- neuropathic pain
- Alzheimer’s disease
- Parkinson’s disease
- type 2 diabetes mellitus
- ifenprodil binding site
- GluN2B-containing NMDA receptor
- stroke
- pancreatic islet cells
- NR1a/NR2B-expressing L(tk-)-cell membrane homogenates
- mouse islet cells
- Inhibitor
- inhibitor
- inhibit