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JTE-607 | mRNA processing inhibitor

JTE-607 (188791-09-5) inhibits inflammatory cytokine production in human peripheral blood mononuclear cells (PBMC’s) without causing immunosuppression: IC50’s = 11 nM (TNF-α), 5.9 nM (IL-1β), 8.8 nM (IL-6), 7.3 nM (IL-8), and 9.1 nM (IL-10).1 It displayed efficacy in a mouse model of septic shock.2 JTE-607 also showed inhibitory activity against acute myelogenous leukemia cell lines.3,4 Recently, the mechanism of action of JTE-607 (a pro-drug, with the active species being the free acid) has been found to be inhibition of pre-messenger RNA endonuclease Cleavage and Polyadenylation Specificity Factor 3 (CPSF3).5,6 This prevents release of newly synthesized mRNA’s resulting in read-through transcription and the formation of DNA-RNA hybrid R-loop structures. Transcripts down-regulated by JTE-607 were related to DNA damage-based phenotype.

1) Kakutani et al. (1999), JTE-607, a novel inflammatory cytokine synthesis inhibitor without immunosuppression, protects from endotoxin shock in mice; Inflamm. Res., 48 461
2) Iwamura et al. (2004), 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., 311 1256
3) Uesato et al. (2006), JTE-607, a multiple cytokine production inhibitor, ameliorates disease in a SCID mouse xenograft acute myeloid leukemia model; Exp. Hematol., 34 1385
4) Tajima et al. (2010), JTE-607, a multiple cytokine production inhibitor, induces apoptosis accompanied by an increase in p21waf1/cip1 in acute myelogenous leukemia cells; Cancer Sci., 101 774
5) Kakegawa et al. (2019), JTE-607, a multiple cytokine production inhibitor, targets CPSF3 and inhibits pre-mRNA; Biochem. Biophys. Res. Commun., 518 32
6) Ross et al. (2020), CPSF3-dependent pre-mRNA processing as a druggable node in AML and Ewing’s sarcoma; Nat. Chem. Biol., 16 50

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Catalog#  10-4842-0005

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Catalog Number:
mRNA processing inhibitor
Chemical Name:
Ethyl (2S)-2-[[3,5-Dichloro-2-hydroxy-4-[2-(4-methylpiperazin-1-yl)ethoxy]benzoyl]amino]-3-phenylpropanoate dihydrochloride
Molecular Weight:
Molecular Formula:
C25H31Cl2N3O5 • 2HCl
Soluble in DMSO (up to 25 mg/ml).
Physical Properties:
White solid
98% by HPLC
NMR (Conforms)
Storage Temperature:
-20° (des.)
Stable for 1 year as supplied. Solutions in DMSO may be stored at -20° for up to 1 month.
Shipping Code:
Materials provided by Focus Biomolecules are for laboratory research use only and are not intended for human or veterinary applications.

Focus BiomoleculesPlymouth Meeting, PA USA1-855-FOCUS21

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