WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 522586
CAS#: 383150-41-2
Description: JTE-013 is a potent, selective sphingosine-1-phosphate 2 (S1P2) receptor antagonist that binds to the human and rat receptors with IC50 values of 17 and 22 nM, respectively, (IC50 values >10 µM for human S1P1 and S1P3).
MedKoo Cat#: 522586
Name: JTE-013
CAS#: 383150-41-2
Chemical Formula: C17H19Cl2N7O
Exact Mass: 407.1028
Molecular Weight: 408.287
Elemental Analysis: C, 50.01; H, 4.69; Cl, 17.37; N, 24.01; O, 3.92
Synonym: JTE-013; JTE 013; JTE013.
IUPAC/Chemical Name: N-(2,6-dichloro-4-pyridinyl)-2-[1,3-dimethyl-4-(1-methylethyl)-1H-pyrazolo[3,4-b]pyridin-6-yl]-hydrazinecarboxamide
InChi Key: RNSLRQNDXRSASX-UHFFFAOYSA-N
InChi Code: InChI=1S/C17H19Cl2N7O/c1-8(2)11-7-14(22-16-15(11)9(3)25-26(16)4)23-24-17(27)20-10-5-12(18)21-13(19)6-10/h5-8H,1-4H3,(H,22,23)(H2,20,21,24,27)
SMILES Code: CC(C1=C2C(N(C)N=C2C)=NC(NNC(NC3=CC(Cl)=NC(Cl)=C3)=O)=C1)C
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
| Biological target: | JTE-013 is a potent and specific S1P2 (Sphingosine-1-Phosphate 2; EDG-5) antagonist. JTE-013 inhibits the specific binding of radiolabeled S1P to human and rat S1P2 with IC50s of 17 nM and 22 nM, respectively. |
| In vitro activity: | This study examined this further and describe lipidomic analysis of AML cells that revealed JTE-013 caused alterations in sphingolipid metabolism, increasing cellular ceramides, dihydroceramides, sphingosine and dihydrosphingosine. Collectively, these findings demonstrate that JTE-013 can have broad off-target effects on sphingolipid metabolism and highlight that caution must be employed in interpreting the use of this reagent in defining the roles of S1P2/4. Reference: Sci Rep. 2022 Jan 10;12(1):454. https://pubmed.ncbi.nlm.nih.gov/35013382/ |
| In vivo activity: | Sepsis rats appeared severe lung injury, indicating that the lung injury induced by sepsis was successfully established. Then, JTE-013 treatment obviously alleviated the lung injury in sepsis rats (Fig. 2A). All these results demonstrated that JTE-013 have protective effects in lung injury induced by sepsis. Reference: J Surg Res. 2021 Sep;265:323-332. https://pubmed.ncbi.nlm.nih.gov/33971464/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMF | 20.0 | 48.99 | |
| DMSO | 60.46 | 148.08 | |
| Ethanol | 34.94 | 85.59 | |
| Ethanol:PBS (pH 7.2) (1:3) | 0.25 | 0.61 |
The following data is based on the product molecular weight 408.287 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | 1. Pitman MR, Lewis AC, Davies LT, Moretti PAB, Anderson D, Creek DJ, Powell JA, Pitson SM. The sphingosine 1-phosphate receptor 2/4 antagonist JTE-013 elicits off-target effects on sphingolipid metabolism. Sci Rep. 2022 Jan 10;12(1):454. doi: 10.1038/s41598-021-04009-w. PMID: 35013382; PMCID: PMC8748775. 2. Lin S, Pandruvada S, Yu H. Inhibition of Sphingosine-1-Phosphate Receptor 2 by JTE013 Promoted Osteogenesis by Increasing Vesicle Trafficking, Wnt/Ca2+, and BMP/Smad Signaling. Int J Mol Sci. 2021 Nov 8;22(21):12060. doi: 10.3390/ijms222112060. PMID: 34769490; PMCID: PMC8584480. 3. Xu Q, Chen J, Zhu Y, Xia W, Liu Y, Xu J. JTE-013 Alleviates Inflammatory Injury and Endothelial Dysfunction Induced by Sepsis In Vivo and In Vitro. J Surg Res. 2021 Sep;265:323-332. doi: 10.1016/j.jss.2021.03.006. Epub 2021 May 7. PMID: 33971464. 4. Kang J, Lee JH, Im DS. Topical Application of S1P2 Antagonist JTE-013 Attenuates 2,4-Dinitrochlorobenzene-Induced Atopic Dermatitis in Mice. Biomol Ther (Seoul). 2020 Nov 1;28(6):537-541. doi: 10.4062/biomolther.2020.036. PMID: 32487782; PMCID: PMC7585635. |
| In vitro protocol: | 1. Pitman MR, Lewis AC, Davies LT, Moretti PAB, Anderson D, Creek DJ, Powell JA, Pitson SM. The sphingosine 1-phosphate receptor 2/4 antagonist JTE-013 elicits off-target effects on sphingolipid metabolism. Sci Rep. 2022 Jan 10;12(1):454. doi: 10.1038/s41598-021-04009-w. PMID: 35013382; PMCID: PMC8748775. 2. Lin S, Pandruvada S, Yu H. Inhibition of Sphingosine-1-Phosphate Receptor 2 by JTE013 Promoted Osteogenesis by Increasing Vesicle Trafficking, Wnt/Ca2+, and BMP/Smad Signaling. Int J Mol Sci. 2021 Nov 8;22(21):12060. doi: 10.3390/ijms222112060. PMID: 34769490; PMCID: PMC8584480. |
| In vivo protocol: | 1. Xu Q, Chen J, Zhu Y, Xia W, Liu Y, Xu J. JTE-013 Alleviates Inflammatory Injury and Endothelial Dysfunction Induced by Sepsis In Vivo and In Vitro. J Surg Res. 2021 Sep;265:323-332. doi: 10.1016/j.jss.2021.03.006. Epub 2021 May 7. PMID: 33971464. 2. Kang J, Lee JH, Im DS. Topical Application of S1P2 Antagonist JTE-013 Attenuates 2,4-Dinitrochlorobenzene-Induced Atopic Dermatitis in Mice. Biomol Ther (Seoul). 2020 Nov 1;28(6):537-541. doi: 10.4062/biomolther.2020.036. PMID: 32487782; PMCID: PMC7585635. |
1: Zhao C, Moreno-Nieves U, Di Battista JA, Fernandes MJ, Touaibia M, Bourgoin SG. Chemical Hypoxia Brings to Light Altered Autocrine Sphingosine-1-Phosphate Signalling in Rheumatoid Arthritis Synovial Fibroblasts. Mediators Inflamm. 2015;2015:436525. doi: 10.1155/2015/436525. Epub 2015 Oct 18. PubMed PMID: 26556954; PubMed Central PMCID: PMC4628658.
2: Liu R, Li X, Qiang X, Luo L, Hylemon PB, Jiang Z, Zhang L, Zhou H. Taurocholate Induces Cyclooxygenase-2 Expression via the Sphingosine 1-phosphate Receptor 2 in a Human Cholangiocarcinoma Cell Line. J Biol Chem. 2015 Dec 25;290(52):30988-1002. doi: 10.1074/jbc.M115.668277. Epub 2015 Oct 30. PubMed PMID: 26518876; PubMed Central PMCID: PMC4692225.
3: Yang L, Han Z, Tian L, Mai P, Zhang Y, Wang L, Li L. Sphingosine 1-Phosphate Receptor 2 and 3 Mediate Bone Marrow-Derived Monocyte/Macrophage Motility in Cholestatic Liver Injury in Mice. Sci Rep. 2015 Sep 1;5:13423. doi: 10.1038/srep13423. PubMed PMID: 26324256; PubMed Central PMCID: PMC4555045.
4: Brünnert D, Piccenini S, Ehrhardt J, Zygmunt M, Goyal P. Sphingosine 1-phosphate regulates IL-8 expression and secretion via S1PR1 and S1PR2 receptors-mediated signaling in extravillous trophoblast derived HTR-8/SVneo cells. Placenta. 2015 Oct;36(10):1115-21. doi: 10.1016/j.placenta.2015.08.010. Epub 2015 Aug 20. PubMed PMID: 26321412.
5: Li MH, Swenson R, Harel M, Jana S, Stolarzewicz E, Hla T, Shapiro LH, Ferrer F. Antitumor Activity of a Novel Sphingosine-1-Phosphate 2 Antagonist, AB1, in Neuroblastoma. J Pharmacol Exp Ther. 2015 Sep;354(3):261-8. doi: 10.1124/jpet.115.224519. Epub 2015 Jun 23. PubMed PMID: 26105954; PubMed Central PMCID: PMC4538871.
6: Japtok L, Schmitz EI, Fayyaz S, Krämer S, Hsu LJ, Kleuser B. Sphingosine 1-phosphate counteracts insulin signaling in pancreatic β-cells via the sphingosine 1-phosphate receptor subtype 2. FASEB J. 2015 Aug;29(8):3357-69. doi: 10.1096/fj.14-263194. Epub 2015 Apr 24. PubMed PMID: 25911610.
7: Lei S, Wang Q, Lv C, Wu C, Yuan Q, Han J. [Inhibition of S1PR2 activity down-regulates expressions of sphingosine kinase 1 and MCP-1 in rat glomerular mesangial cells under high glucose]. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2015 Jan;31(1):36-9. Chinese. PubMed PMID: 25575056.
8: Oskeritzian CA, Hait NC, Wedman P, Chumanevich A, Kolawole EM, Price MM, Falanga YT, Harikumar KB, Ryan JJ, Milstien S, Sabbadini R, Spiegel S. The sphingosine-1-phosphate/sphingosine-1-phosphate receptor 2 axis regulates early airway T-cell infiltration in murine mast cell-dependent acute allergic responses. J Allergy Clin Immunol. 2015 Apr;135(4):1008-18.e1. doi: 10.1016/j.jaci.2014.10.044. Epub 2014 Dec 13. PubMed PMID: 25512083; PubMed Central PMCID: PMC4388821.
9: Wang Z, Sims CR, Patil NK, Gokden N, Mayeux PR. Pharmacologic targeting of sphingosine-1-phosphate receptor 1 improves the renal microcirculation during sepsis in the mouse. J Pharmacol Exp Ther. 2015 Jan;352(1):61-6. doi: 10.1124/jpet.114.219394. Epub 2014 Oct 29. PubMed PMID: 25355645; PubMed Central PMCID: PMC4279105.
10: Li MH, Harel M, Hla T, Ferrer F. Induction of chemokine (C-C motif) ligand 2 by sphingosine-1-phosphate signaling in neuroblastoma. J Pediatr Surg. 2014 Aug;49(8):1286-91. doi: 10.1016/j.jpedsurg.2014.04.001. Epub 2014 May 16. PubMed PMID: 25092091; PubMed Central PMCID: PMC4122984.
11: Liu R, Zhao R, Zhou X, Liang X, Campbell DJ, Zhang X, Zhang L, Shi R, Wang G, Pandak WM, Sirica AE, Hylemon PB, Zhou H. Conjugated bile acids promote cholangiocarcinoma cell invasive growth through activation of sphingosine 1-phosphate receptor 2. Hepatology. 2014 Sep;60(3):908-18. doi: 10.1002/hep.27085. Epub 2014 Jul 28. PubMed PMID: 24700501; PubMed Central PMCID: PMC4141906.
12: Wang XQ, Mao LJ, Fang QH, Kobayashi T, Kim HJ, Sugiura H, Kawasaki S, Togo S, Kamio K, Liu X, Rennard SI. Sphingosylphosphorylcholine induces α-smooth muscle actin expression in human lung fibroblasts and fibroblast-mediated gel contraction via S1P2 receptor and Rho/Rho-kinase pathway. Prostaglandins Other Lipid Mediat. 2014 Jan;108:23-30. doi: 10.1016/j.prostaglandins.2014.02.002. Epub 2014 Mar 5. PubMed PMID: 24614064.
13: Guan Z, Singletary ST, Cook AK, Hobbs JL, Pollock JS, Inscho EW. Sphingosine-1-phosphate evokes unique segment-specific vasoconstriction of the renal microvasculature. J Am Soc Nephrol. 2014 Aug;25(8):1774-85. doi: 10.1681/ASN.2013060656. Epub 2014 Feb 27. PubMed PMID: 24578134; PubMed Central PMCID: PMC4116055.
14: Kamiya T, Nagaoka T, Omae T, Yoshioka T, Ono S, Tanano I, Yoshida A. Role of Ca2+ -dependent and Ca2+ -sensitive mechanisms in sphingosine 1-phosphate-induced constriction of isolated porcine retinal arterioles in vitro. Exp Eye Res. 2014 Apr;121:94-101. doi: 10.1016/j.exer.2014.01.011. Epub 2014 Jan 31. PubMed PMID: 24486793.
15: Schaper K, Kietzmann M, Bäumer W. Sphingosine-1-phosphate differently regulates the cytokine production of IL-12, IL-23 and IL-27 in activated murine bone marrow derived dendritic cells. Mol Immunol. 2014 May;59(1):10-8. doi: 10.1016/j.molimm.2013.11.015. Epub 2014 Jan 14. PubMed PMID: 24434636.
16: Fayyaz S, Henkel J, Japtok L, Krämer S, Damm G, Seehofer D, Püschel GP, Kleuser B. Involvement of sphingosine 1-phosphate in palmitate-induced insulin resistance of hepatocytes via the S1P2 receptor subtype. Diabetologia. 2014 Feb;57(2):373-82. doi: 10.1007/s00125-013-3123-6. Epub 2013 Nov 29. PubMed PMID: 24292566.
17: Kendig DM, Matsumoto AK, Moreland RS. Sphingosine-1-phosphate induced contraction of bladder smooth muscle. Eur J Pharmacol. 2013 Nov 15;720(1-3):355-62. doi: 10.1016/j.ejphar.2013.10.004. Epub 2013 Oct 10. PubMed PMID: 24120660; PubMed Central PMCID: PMC3849345.
18: Satsu H, Schaeffer MT, Guerrero M, Saldana A, Eberhart C, Hodder P, Cayanan C, Schürer S, Bhhatarai B, Roberts E, Rosen H, Brown SJ. A sphingosine 1-phosphate receptor 2 selective allosteric agonist. Bioorg Med Chem. 2013 Sep 1;21(17):5373-82. doi: 10.1016/j.bmc.2013.06.012. Epub 2013 Jun 15. PubMed PMID: 23849205; PubMed Central PMCID: PMC3786410.
19: Liu Y, Saiyan S, Men TY, Gao HY, Wen C, Liu Y, Zhou X, Wu CT, Wang LS, Cui CP. Hepatopoietin Cn reduces ethanol-induced hepatoxicity via sphingosine kinase 1 and sphingosine 1-phosphate receptors. J Pathol. 2013 Aug;230(4):365-76. doi: 10.1002/path.4194. PubMed PMID: 23839903.
20: Zhang G, Yang L, Kim GS, Ryan K, Lu S, O'Donnell RK, Spokes K, Shapiro N, Aird WC, Kluk MJ, Yano K, Sanchez T. Critical role of sphingosine-1-phosphate receptor 2 (S1PR2) in acute vascular inflammation. Blood. 2013 Jul 18;122(3):443-55. doi: 10.1182/blood-2012-11-467191. Epub 2013 May 30. PubMed PMID: 23723450; PubMed Central PMCID: PMC3716205.
