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Chemical Structure| 909725-61-7 Chemical Structure| 909725-61-7

Structure of W146
CAS No.: 909725-61-7

Chemical Structure| 909725-61-7

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W146 is a selective antagonist of sphingosine-1-phosphate receptor 1 (S1PR1) with an EC50 value of 398 nM.

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Product Details of W146

CAS No. :909725-61-7
Formula : C16H27N2O4P
M.W : 342.37
SMILES Code : O=C(NC1=CC=CC(CCCCCC)=C1)[C@H](N)CCP(O)(O)=O
MDL No. :MFCD16875441

Safety of W146

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

Related Pathways of W146

GPCR

Isoform Comparison

Biological Activity

In Vitro:

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. Vet Res. 2022 Jul 19;53(1):58
Mouse glomerular endothelial cells 1 µM 3 days Chronic S1P1R antagonism significantly reduced HSP27 mRNA expression Kidney Int. 2014 Apr;85(4):807-23
Human umbilical vein endothelial cells 1 µM 3 days Chronic S1P1R antagonism significantly reduced HSP27 mRNA expression Kidney Int. 2014 Apr;85(4):807-23
Rat sensory neurons 1 µM 30 minutes 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

In Vivo:

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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2.92mL

0.58mL

0.29mL

14.60mL

2.92mL

1.46mL

29.21mL

5.84mL

2.92mL

 

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