WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 530225
CAS#: 188791-09-5 (HCl)
Description: JTE-607, also known as TO-207, is a cytokine production inhibitor potentially for the treatment of systemic inflammatory response, and induces apoptosis accompanied by an increase in p21waf1/cip1 in acute myelogenous leukemia cells.
MedKoo Cat#: 530225
Name: JTE-607 HCl
CAS#: 188791-09-5 (HCl)
Chemical Formula: C25H33Cl4N3O5
Exact Mass:
Molecular Weight: 597.355
Elemental Analysis: C, 50.27; H, 5.57; Cl, 23.74; N, 7.03; O, 13.39
Related CAS #: 188791-71-1 (free base) 188791-09-5 (HCl)
Synonym: TO-207; TO 207; TO207; JTE-607; JTE 607; JTE 607; JTE-607 HCl; JTE-607 dihydrochloride.
IUPAC/Chemical Name: N-[3,5-Dichloro-2-hydroxy-4-[2-(4-methyl-1-piperazinyl)ethoxy]benzoyl]-L-phenylalanine ethyl ester dihydrochloride
InChi Key: JUJAUEQJEWIWCQ-FJSYBICCSA-N
InChi Code: InChI=1S/C25H31Cl2N3O5.2ClH/c1-3-34-25(33)20(15-17-7-5-4-6-8-17)28-24(32)18-16-19(26)23(21(27)22(18)31)35-14-13-30-11-9-29(2)10-12-30;;/h4-8,16,20,31H,3,9-15H2,1-2H3,(H,28,32);2*1H/t20-;;/m0../s1
SMILES Code: O=C(OCC)[C@H](CC1=CC=CC=C1)NC(C2=CC(Cl)=C(OCCN3CCN(C)CC3)C(Cl)=C2O)=O.[H]Cl.[H]Cl
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
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-607 is a highly selective inflammatory cytokine synthesis inhibitor that inhibits inflammatory cytokine production, including TNF-α, IL-1β, IL-6, IL-8 and IL-10, from LPS-stimulated human PBMCs, with IC50s of 11, 5.9, 8.8, 7.3 and 9.1 nM, respectively. |
| In vitro activity: | The suppressive effect of JTE-607 was characterized on the growth of AML cells in terms of apoptosis and cell-cycle arrest at the molecular level. To evaluate whether JTE-607 induces apoptosis, U-937 cells cultured in the presence or absence of JTE-607 were stained with FITC-conjugated anti-Annexin V and PI. The result of flow cytometry analysis showed that Annexin V-positive/PI-negative apoptotic cells and PI-positive necrotic cells emerged after a 2-day exposure to JTE-607, and the proportion of those cells was increased concentration dependently. In the cell-cycle analysis, the proportion of the cells in the S-phase was increased when U-937 cells were exposed to over 0.1–0.3 μm of JTE-607 for 1 day. A significant decrease in c-Myc and an increase in p21waf1/cip1 occurred after 2–48 h exposure with JTE-607. Together, these results suggest that JTE-607 exerts its antiproliferative effect against AML cells through the sequential process including cell-cycle arrest at the S-phase and induction of apoptotic cell death. Reference: Cancer Sci. 2010 Mar;101(3):774-81. https://pubmed.ncbi.nlm.nih.gov/20028380/ |
| In vivo activity: | Mice bearing established leukemia were injected with JTE-607 at 100 mg/kg on day 18 and sacrificed 1h after the injection. Human cytokine mRNA levels in the bone marrow cells were then determined by quantitative RT-PCR and normalized to human GAPDH mRNA levels. The results show that single injection of JTE-607 dramatically and rapidly reduced human IL-6 and IL-8 mRNA; in contrast, human GAPDH mRNA levels were not altered. Moreover, it was observed that human VEGF mRNA levels were also reduced to a lesser extent than the two proinflammatory cytokines. In aggregate, these data indicate that JTE-607 is able to suppress both the growth and accompanying cytokine/growth factor production from AML cells significantly in an in vivo milieu. Reference: Cancer Sci. 2010 Mar;101(3):774-81. https://pubmed.ncbi.nlm.nih.gov/20028380/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 136.58 | 228.64 | |
| H2O | 179.74 | 300.89 |
The following data is based on the product molecular weight 597.355 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. Tajima N, Fukui K, Uesato N, Maruhashi J, Yoshida T, Watanabe Y, Tojo A. JTE-607, a multiple cytokine production inhibitor, induces apoptosis accompanied by an increase in p21waf1/cip1 in acute myelogenous leukemia cells. Cancer Sci. 2010 Mar;101(3):774-81. doi: 10.1111/j.1349-7006.2009.01446.x. Epub 2009 Nov 18. PMID: 20028380. 2. Kakegawa J, Sakane N, Suzuki K, Yoshida T. JTE-607, a multiple cytokine production inhibitor, targets CPSF3 and inhibits pre-mRNA processing. Biochem Biophys Res Commun. 2019 Oct 8;518(1):32-37. doi: 10.1016/j.bbrc.2019.08.004. Epub 2019 Aug 6. PMID: 31399191. 3.Asaga T, Ueki M, Chujo K, Taie S. JTE-607, an inflammatory cytokine synthesis inhibitor, attenuates ischemia/reperfusion-induced renal injury by reducing neutrophil activation in rats. J Biosci Bioeng. 2008 Jul;106(1):22-6. doi: 10.1263/jbb.106.22. PMID: 18691526. |
| In vitro protocol: | 1. Tajima N, Fukui K, Uesato N, Maruhashi J, Yoshida T, Watanabe Y, Tojo A. JTE-607, a multiple cytokine production inhibitor, induces apoptosis accompanied by an increase in p21waf1/cip1 in acute myelogenous leukemia cells. Cancer Sci. 2010 Mar;101(3):774-81. doi: 10.1111/j.1349-7006.2009.01446.x. Epub 2009 Nov 18. PMID: 20028380. 2. Kakegawa J, Sakane N, Suzuki K, Yoshida T. JTE-607, a multiple cytokine production inhibitor, targets CPSF3 and inhibits pre-mRNA processing. Biochem Biophys Res Commun. 2019 Oct 8;518(1):32-37. doi: 10.1016/j.bbrc.2019.08.004. Epub 2019 Aug 6. PMID: 31399191. |
| In vivo protocol: | 1. Tajima N, Fukui K, Uesato N, Maruhashi J, Yoshida T, Watanabe Y, Tojo A. JTE-607, a multiple cytokine production inhibitor, induces apoptosis accompanied by an increase in p21waf1/cip1 in acute myelogenous leukemia cells. Cancer Sci. 2010 Mar;101(3):774-81. doi: 10.1111/j.1349-7006.2009.01446.x. Epub 2009 Nov 18. PMID: 20028380. 2. Asaga T, Ueki M, Chujo K, Taie S. JTE-607, an inflammatory cytokine synthesis inhibitor, attenuates ischemia/reperfusion-induced renal injury by reducing neutrophil activation in rats. J Biosci Bioeng. 2008 Jul;106(1):22-6. doi: 10.1263/jbb.106.22. PMID: 18691526. |
1: Borozdenkova S, Mant TG, Allen E, Pu K, Hoshino S, Jurcevic S. Effects of a cytokine inhibitor, JTE-607, on the response to endotoxin in healthy human volunteers. Int Immunopharmacol. 2011 Nov;11(11):1837-43. doi: 10.1016/j.intimp.2011.07.013. PubMed PMID: 21820084.
2: Tajima N, Fukui K, Uesato N, Maruhashi J, Yoshida T, Watanabe Y, Tojo A. JTE-607, a multiple cytokine production inhibitor, induces apoptosis accompanied by an increase in p21waf1/cip1 in acute myelogenous leukemia cells. Cancer Sci. 2010 Mar;101(3):774-81. doi: 10.1111/j.1349-7006.2009.01446.x. PubMed PMID: 20028380.
3: Asaga T, Ueki M, Chujo K, Taie S. JTE-607, an inflammatory cytokine synthesis inhibitor, attenuates ischemia/reperfusion-induced renal injury by reducing neutrophil activation in rats. J Biosci Bioeng. 2008 Jul;106(1):22-6. doi: 10.1263/jbb.106.22. PubMed PMID: 18691526.
4: Uesato N, Fukui K, Maruhashi J, Tojo A, Tajima N. JTE-607, a multiple cytokine production inhibitor, ameliorates disease in a SCID mouse xenograft acute myeloid leukemia model. Exp Hematol. 2006 Oct;34(10):1385-92. PubMed PMID: 16982331.
5: Iwamura H, Sato M, Wakitani K. Comparative study of glucocorticoids, cyclosporine A, and JTE-607 [(-)-Ethyl-N[3,5-dichloro-2-hydroxy-4-[2-(4-methylpiperazin-1-yl)ethoxy]benzoyl]- L-phenylalaninate dihydrochloride] in a mouse septic shock model. J Pharmacol Exp Ther. 2004 Dec;311(3):1256-63. PubMed PMID: 15280441.
6: Ryugo M, Sawa Y, Ono M, Miyamoto Y, Aleshin AN, Matsuda H. Pharmacologic preconditioning of JTE-607, a novel cytokine inhibitor, attenuates ischemia-reperfusion injury in the myocardium. J Thorac Cardiovasc Surg. 2004 Jun;127(6):1723-7. PubMed PMID: 15173729.
7: Jian MY, Koizumi T, Tsushima K, Kubo K. JTE-607, a cytokine release blocker, attenuates acid aspiration-induced lung injury in rats. Eur J Pharmacol. 2004 Mar 19;488(1-3):231-8. PubMed PMID: 15044056.
8: Iwamura H, Inushima K, Takeuchi K, Kakutani M, Wakitani K. Prophylactic effect of JTE-607 on LPS-induced acute lung injury in rats with CINC-1 inhibition. Inflamm Res. 2002 Mar;51(3):160-6. PubMed PMID: 12005207.
9: Kakutani M, Takeuchi K, Waga I, Iwamura H, Wakitani K. JTE-607, a novel inflammatory cytokine synthesis inhibitor without immunosuppression, protects from endotoxin shock in mice. Inflamm Res. 1999 Aug;48(8):461-8. PubMed PMID: 10493164.
10: Sasaki J, Fujishima S, Iwamura H, Wakitani K, Aiso S, Aikawa N. Prior burn insult induces lethal acute lung injury in endotoxemic mice: effects of cytokine inhibition. Am J Physiol Lung Cell Mol Physiol. 2003 Feb;284(2):L270-8. PubMed PMID: 12388363.
Related CAS #
188791-71-1 (JTE-607 Free base)
188791-09-5 (JTE-607 HCl)
