JTE-607 dihydrochloride | CAS#188791-09-5 | 188791-71-1 | cytokine production inhibitor

MedKoo Cat#: 530225 | Name: JTE-607 HCl

Description:

WARNING: This product is for research use only, not for human or veterinary use.

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.

Chemical Structure

JTE-607 HCl

CAS#188791-09-5 (HCl)

Theoretical Analysis

MedKoo Cat#: 530225

Name: JTE-607 HCl

CAS#: 188791-09-5 (HCl)

Chemical Formula: C25H33Cl4N3O5

Exact Mass: 0.0000

Molecular Weight: 597.36

Elemental Analysis: C, 50.27; H, 5.57; Cl, 23.74; N, 7.03; O, 13.39

Price and Availability

Size	Price	Availability
5mg	USD 90.00	Ready to ship
10mg	USD 150.00	Ready to ship
25mg	USD 250.00	Ready to ship
50mg	USD 450.00	Ready to ship
100mg	USD 750.00	Ready to ship
200mg	USD 1,350.00	Ready to ship

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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

More Info

Related CAS # 188791-71-1 (JTE-607 Free base) 188791-09-5 (JTE-607 HCl)

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#C23R04B26

View CoA: current batch, Lot# C22R01B27

QC Data

View QC data: current batch, Lot# C22R01B27

View QC data: current batch, Lot#C23R04B26

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

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	mg/mL	mM
Solubility
	DMSO	136.6	228.64
	H2O	179.7	300.89

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 597.36 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:

In vivo protocol:

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.