Description
Sphingosine-
1-
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-
coupled receptors, S1P
1/EDG-
1, S1P
2/EDG-
5, S1P
3/EDG-
3, S1P
4/EDG-
6, and S1P
5/EDG-
8. JTE-
013 is a potent, selective sphingosine-
1-
phosphate 2 (S1P
2) receptor antagonist that binds to the human and rat receptors with IC
50 values of 17 and 22 nM, respectively, (IC
50 values >10 μM for human S1P
1 and S1P
3). It reverses the inhibitory effects of S1P on cell migration of vascular endothelial cells and smooth muscle cells. Similarly, JTE-
013 reverses the inhibition of S1P on invasion and migration of B16 melanoma cells. JTE-
013 inhibits S1P-
induced contraction of, as well as cyclic AMP accumulation in, coronary artery smooth muscle cells.
Uses
JTE-013 has been used in
in vitro bloodbrain barrier (BBB) and bloodtumor barrier (BTB) assays.
Definition
ChEBI: 1-(2,6-dichloro-4-pyridinyl)-3-[(1,3-dimethyl-4-propan-2-yl-6-pyrazolo[3,4-b]pyridinyl)amino]urea is a pyrazolopyridine.
Biochem/physiol Actions
JTE-013 can enhance the excitability of small-diameter sensory neurons. It has the ability to repress sphingosine 1-phosphate (S1P)-mediated cellular migration.
References
[1] MELISSA R PITMAN. The sphingosine 1-phosphate receptor 2/4 antagonist JTE-013 elicits off-target effects on sphingolipid metabolism.[J]. Scientific Reports, 2022: 454. DOI:
10.1038/s41598-021-04009-w[2] MAKOTO OSADA. Enhancement of sphingosine 1-phosphate-induced migration of vascular endothelial cells and smooth muscle cells by an EDG-5 antagonist[J]. Biochemical and biophysical research communications, 2002, 299 3: Pages 483-487. DOI:
10.1016/s0006-291x(02)02671-2[3] KAYO ARIKAWA. Ligand-dependent inhibition of B16 melanoma cell migration and invasion via endogenous S1P2 G protein-coupled receptor. Requirement of inhibition of cellular RAC activity.[J]. The Journal of Biological Chemistry, 2003, 278 35: 32841-32851. DOI:
10.1074/jbc.m305024200[4] QIUMIN XU BMED . JTE-013 Alleviates Inflammatory Injury and Endothelial Dysfunction Induced by Sepsis In Vivo and In Vitro[J]. Journal of Surgical Research, 2021, 265: Pages 323-332. DOI:
10.1016/j.jss.2021.03.006[5] MENGDIE WANG. Inhibition of sphingosine 1-phosphate (S1P) receptor 1/2/3 ameliorates biological dysfunction in rheumatoid arthritis fibroblast-like synoviocyte MH7A cells through Gαi/Gαs rebalancing[J]. Clinical and Experimental Pharmacology and Physiology, 2021, 48 8: 1080-1089. DOI:
10.1111/1440-1681.13460[6] STEPHANIE S DUSABAN. Sphingosine 1-phosphate receptor 3 and RhoA signaling mediate inflammatory gene expression in astrocytes.[J]. Journal of Neuroinflammation, 2017: 111. DOI:
10.1186/s12974-017-0882-x[7] NADINE AL ALAM Sawsan I K. FTY720P inhibits hepatic Na(+)-K(+) ATPase via S1PR2 and PGE2.[J]. Biochemistry and Cell Biology, 2016, 94 4: 371-377. DOI:
10.1139/bcb-2016-0025
