W146 TFA

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

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

Signaling Pathways >> GPCR/G Protein >> LPL Receptor

Research Areas >> Metabolic Disease

EC50: 398 nM (S1PR1)[1].

W146 is a S1PR1 antagonist with a Ki of ~70-80 nM[1]. W146 pretreatment significantly increases activated cleaved caspase-3 levels. The reduced EPCs apoptosis which 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.

W146 (5 mg/kg, ip, prior to AMD3100 administration) pre-treatment shows approximately 8-fold increase of KSL-HSPC mobilization, measured by the CFU-G/M colony forming assays, compared to that in mice treated with AMD3100 alone[3] The W146-mediated augmentation of KSL-HSPC mobilization is specific, because pretreatment of mice with W140 is unable to produce any effect on AMD3100-stimulated KSL-HSPC mobilization. Injections of W146, W140, JTE013, or Cay10444 do not alter the basal WBC count in mice[3]. Animal Model: Mice (4-6-week-old)[3] . Dosage: 5 mg/kg. Administration: IP, 1 hour prior to AMD3100 (ADM) administration. Result: Significantly increased in KSL-HSPC mobilization compared to that in mice pretreated with dextran followed by AMD3100 administration.

[1]. M Germana Sanna, et al. Enhancement of capillary leakage and restoration of lymphocyte egress by a chiral S1P1 antagonist in vivo. Nat Chem Biol. 2006 Aug;2(8):434-41. Epub 2006 Jul 9.

[2]. Jingjing Liu, et al. 3-amino-4-(3-hexylphenylamino)-4-oxobutyl phosphonic acid (W146), a Selective Antagonist of Sphingosine-1-phospahte Receptor Subtype 1, Enhances AMD3100-stimulated Mobilization of Hematopoietic Stem Progenitor Cells in Animals. J Biochem Pharmacol Res. 2013 Dec; 1(4): 197–203.

[3]. Hang Wang, et al. Sphingosine-1-phosphate promotes the proliferation and attenuates apoptosis of Endothelial progenitor cells via S1PR1/S1PR3/PI3K/Akt pathway. Cell Biol Int. 2018 May 23.