W146 is a selective antagonist of sphingosine-1-phosphate receptor 1 (S1PR1) with an EC50 value of 398 nM.
W146 细胞实验
Cell Line
Concentration
Treated Time
Description
References
BV-2 microglial cells
250 nM
1 hour
To investigate the effect of W146 on LPS-induced pSTAT3 expression in BV-2 microglial cells. Results showed that W146 pretreatment could inhibit LPS-induced increase in pSTAT3 expression.
J Headache Pain. 2022 Feb 10;23(1):25
DF-1 chicken fibroblasts
10 µM/mL
1-hour pretreatment followed by 24-hours infection
To investigate the inhibitory effect of W146 on NDV-induced IL-1β expression, results showed that W146 significantly reduced GM-induced IL-1β protein expression.
W146, as a selective antagonist for S1PR1, in combination with CAY10444 (S1PR3 antagonist), blocked the S1P-induced enhancement of neuronal excitability.
J Neuroinflammation. 2015 Apr 12;12:70
W146 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice
C57BL/6 mice
Intraperitoneal injection
0.1 mg/kg
Once daily for 3 days
Chronic S1P1R antagonism exacerbated renal and hepatic injury and reduced endothelial HSP27 expression
Kidney Int. 2014 Apr;85(4):807-23
C57BL/6J mice
LPS/GalN-induced acute liver failure model
Intraperitoneal injection
0.1 mg/kg
10 minutes before and 30 minutes after the LPS/GalN injection
To evaluate the effect of S1PR1 inhibition on acute liver failure. Results showed that S1PR1 inhibition did not significantly improve liver damage but reduced serum TNF-α and IL-6 levels and partially attenuated the phosphorylation of MAPKs signaling.
United European Gastroenterol J. 2016 Oct;4(5):677-685
Sprague Dawley rats
Thermal hyperalgesia model
Intraplantar injection
0.1–0.6 μg
Single injection, 15 minutes before S1P injection
W146 dose-dependently blocked S1P-induced thermal hyperalgesia, while its inactive enantiomer W140 had no such effect
Pain. 2011 Mar;152(3):643-648
Rats
Paclitaxel-induced neuropathic pain model
Intrathecal injection
0.2-2.2 nmol/day
Daily administration for 15 days
W146 blocked and reversed paclitaxel-induced neuropathic pain by inhibiting spinal neuroinflammatory processes
J Biol Chem. 2014 Jul 25;289(30):21082-97
Sprague-Dawley rats
BPH model
Intraprostatic injection
0.5 nmol
4 weeks
W-146 suppresses testosterone-induced BPH
iScience. 2024 Oct 30;27(12):111290
C57BL/6 J mice
Chronic migraine model
Intraperitoneal injection
1 mg/kg
Once daily for 9 days
To investigate the effect of W146 on chronic NTG-induced hyperalgesia. Results showed that W146 alleviated NTG-induced mechanical and thermal hyperalgesia and suppressed the upregulation of CGRP and c-fos in the TCC.
J Headache Pain. 2022 Feb 10;23(1):25
C57BL/6J mice
Pilocarpine-induced status epilepticus model and pentylenetetrazol-induced epilepsy model
Intraperitoneal injection
1 mg/kg
Once daily for 48 hours
W146 increased the level of tight junction protein, attenuated blood-brain barrier disruption, and reduced seizure severity.
Neural Regen Res. 2023 Aug;18(8):1763-1769
Mice
Experimental Autoimmune Encephalomyelitis (EAE) model
Intraperitoneal injection
1 mg/kg
Daily administration for 14 days
W146 is a selective S1PR1 antagonist used to study the analgesic mechanism of fingolimod. The experiments showed that W146 could block the inhibitory effect of fingolimod on EAE-induced hyperalgesia.
Pain. 2018 Feb;159(2):224-238
Syrian hamster
Hibernation model
Intracardial injection
5 mg/kg
Single dose
Blockade of S1P1 receptor precludes restoration of lymphocyte numbers upon arousal
Proc Natl Acad Sci U S A. 2011 Feb 1;108(5):2052-7
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