W146 (trifluoroacetate salt)

• CAT Number: R026441
• CAS Number: 909725-62-8
• Molecular Formula: C16H27N2O4P • CF3COOH
• Molecular Weight: 456.4
• Purity: ≥95%
• Storage: -20°C
• InChI: InChI=1S/C16H27N2O4P.C2HF3O2/c1-2-3-4-5-7-13-8-6-9-14(12-13)18-16(19)15(17)10-11-23(20,21)22;3-2(4,5)1(6)7/h6,8-9,12,15H,2-5,7,10-11,17H2,1H3,(H,18,19)(H2,20,21,22);(H,6,7)/t15-;/m1./s1
• InChIKey: JDWCNCPWPLHFEX-XFULWGLBSA-N
• SMILES: CCCCCCC1=CC=CC(NC([C@H](N)CCP(O)(O)=O)=O)=C1.FC(F)(C(O)=O)F

Sphingosine-<wbr></wbr>1-<wbr></wbr>phosphate (S1P) is a bioactive lipid that exhibits a broad spectrum of biological activities including cell proliferation, survival, migration, cytoskeletal organization, and morphogenesis. It exerts its activity by binding to five distinct G protein-<wbr></wbr>coupled receptors, S1P1/EDG-<wbr></wbr>1, S1P2/EDG-<wbr></wbr>5, S1P3/EDG-<wbr></wbr>3, S1P4/EDG-<wbr></wbr>6, and S1P5/EDG-<wbr></wbr>8. W146 is a S1P1 receptor antagonist that exhibits a Ki value of 77 nM for the human receptor in a GTP-<wbr></wbr>γS binding assay with equipotency at the murine S1P1 receptor (2a = W146; 2b = W140 in supplemental material). No agonist or antagonist activity was observed at 10 µM W146 at S1P2, S1P3, or S1P5 receptors. W146 is active in vivo causing skin capillary leakage in murine lung and skin as well as inhibition of S1P1 agonist-<wbr></wbr>induced lymphocyte sequestration. The half-<wbr></wbr>life of W146 in rat blood is 73 minutes.

Reference

1.Takuwa, Y.,Takuwa, N., and Sugimoto, N. The Edg family G protein-coupled receptors for lysophospholipids: Their signaling properties and biological activities. Journal of Biochemistry 131, 767-771 (2002).