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

W146 is a S1PR1 antagonist with a K i of ~70-80 nM [1]. W146 pretreatment significantly increases activated cleaved caspase-3 levels. The reduced apoptosis of EPCs induced by S1P is completely abolished after treatment with W146 [2]. Apoptosis Analysis [2] Cell Line: Endothelial progenitor cells (EPCs). Concentration: 10 μM. Incubation Time: 30 min before the addition of S1P. Result: Increases activated cleaved caspase-3 levels.

Pre-treatment with W146 (5 mg/kg, intraperitoneally (ip), before AMD3100 administration) significantly enhances KSL-HSPC mobilization, showcasing an approximately 8-fold increase, as determined by CFU-G/M colony forming assays, in comparison with the effects observed in mice receiving only AMD3100. This effect of W146 on enhancing KSL-HSPC mobilization is notably specific; contrasting results are seen with W140 pretreatment, which does not influence AMD3100-induced KSL-HSPC mobilization. Notably, administrations of W146, W140, JTE013, or Cay10444 do not impact the basal white blood cell (WBC) count in mice. The experiments were conducted on 4-6-week-old mice, utilizing a dosage of 5 mg/kg administered via IP 1 hour before the AMD3100 (ADM) treatment, leading to a marked increase in KSL-HSPC mobilization compared to the control group treated with dextran followed by AMD3100.