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Details

Stereochemistry ABSOLUTE
Molecular Formula C25H31Cl2N3O5
Molecular Weight 524.437
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of JTE-607 FREE BASE

SMILES

CCOC(=O)[C@H](CC1=CC=CC=C1)NC(=O)C2=CC(Cl)=C(OCCN3CCN(C)CC3)C(Cl)=C2O

InChI

InChIKey=IPSSXIMJJXSJQB-FQEVSTJZSA-N
InChI=1S/C25H31Cl2N3O5/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)/t20-/m0/s1

HIDE SMILES / InChI

Molecular Formula C25H31Cl2N3O5
Molecular Weight 524.437
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

JTE-607 is a multiple cytokine inhibitor. JTE-607 inhibited inflammatory cytokine production, including tumour necrosis factor (TNF)-alpha, interleukin IL-1beta, IL-6, IL-8, and IL-10, from LPS-stimulated human PBMCs. This compound may be useful for the treatment of various cytokine-mediated diseases such as septic shock without causing immunosuppression. JTE-607 may thus be efficacious in cytokine-mediated lung inflammation such as acute respiratory distress syndrome. JTE-607 inhibits the production of IL-10, IL-1ra and C-reactive protein in a human model of endotoxemia. In a leukaemia model engrafted with U-937 cells, JTE-607 significantly prolonged survival in mice and reduced human cytokine mRNA levels in the bone marrow. These results suggest the usefulness of JTE-607 in therapeutic applications for patients with hypercytokinemia and aggressive acute myelogenous leukaemia cell proliferation. JTE-607 had been in phase II clinical trials for the treatment of systemic inflammatory response syndrome but this study was discontinued.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Preventing
Unknown

Approved Use

Unknown
Doses

Doses

DosePopulationAdverse events​
0.3 mg/kg single, intravenous (unknown)
Highest studied dose
Dose: 0.3 mg/kg
Route: intravenous
Route: single
Dose: 0.3 mg/kg
Sources:
healthy
n = 6
Health Status: healthy
Sex: M
Food Status: FASTED
Population Size: 6
Sources:
PubMed

PubMed

TitleDatePubMed
JTE-607, a novel inflammatory cytokine synthesis inhibitor without immunosuppression, protects from endotoxin shock in mice.
1999 Aug
Prophylactic effect of JTE-607 on LPS-induced acute lung injury in rats with CINC-1 inhibition.
2002 Mar
Prior burn insult induces lethal acute lung injury in endotoxemic mice: effects of cytokine inhibition.
2003 Feb
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.
2004 Dec
Pharmacologic preconditioning of JTE-607, a novel cytokine inhibitor, attenuates ischemia-reperfusion injury in the myocardium.
2004 Jun
JTE-607, a cytokine release blocker, attenuates acid aspiration-induced lung injury in rats.
2004 Mar 19
JTE-607, a multiple cytokine production inhibitor, ameliorates disease in a SCID mouse xenograft acute myeloid leukemia model.
2006 Oct
JTE-607, an inflammatory cytokine synthesis inhibitor, attenuates ischemia/reperfusion-induced renal injury by reducing neutrophil activation in rats.
2008 Jul
JTE-607, a multiple cytokine production inhibitor, induces apoptosis accompanied by an increase in p21waf1/cip1 in acute myelogenous leukemia cells.
2010 Mar
Effects of a cytokine inhibitor, JTE-607, on the response to endotoxin in healthy human volunteers.
2011 Nov
Patents

Sample Use Guides

0.03, 0.1 or 0.3 mg/kg/h a single 8-hour infusion
Route of Administration: Intravenous
U-937 and HL-60 cells were exposed to 0.01–1 uM of JTE-607 for 2 h in the measurement of cytokine mRNA levels or 24 h to determine cytokine protein levels in the culture supernatant. IL-6 and IL-8 mRNA levels were reduced by JTE-607 from a concentration of 0.1 uM in both cell lines.
Substance Class Chemical
Created
by admin
on Sat Dec 16 08:42:12 GMT 2023
Edited
by admin
on Sat Dec 16 08:42:12 GMT 2023
Record UNII
UBL69S77S3
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
JTE-607 FREE BASE
Common Name English
L-PHENYLALANINE, N-(3,5-DICHLORO-2-HYDROXY-4-(2-(4-METHYL-1-PIPERAZINYL)ETHOXY)BENZOYL)-, ETHYL ESTER
Systematic Name English
Code System Code Type Description
CAS
188791-71-1
Created by admin on Sat Dec 16 08:42:12 GMT 2023 , Edited by admin on Sat Dec 16 08:42:12 GMT 2023
PRIMARY
PUBCHEM
9938545
Created by admin on Sat Dec 16 08:42:12 GMT 2023 , Edited by admin on Sat Dec 16 08:42:12 GMT 2023
PRIMARY
FDA UNII
UBL69S77S3
Created by admin on Sat Dec 16 08:42:12 GMT 2023 , Edited by admin on Sat Dec 16 08:42:12 GMT 2023
PRIMARY
Related Record Type Details
ACTIVE MOIETY