JTE-607

JTE-607, a highly selective inflammatory cytokine synthesis inhibitor, protects from endotoxin shock in mice. JTE-607 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. Cleavage and Polyadenylation Specificity Factor 3 (CPSF3) is the target of JTE-607.

Product information

CAS Number: 188791-09-5

Molecular Weight: 597.36

Formula: C25H33Cl4N3O5

Chemical Name: ethyl (2S)-2-({3, 5-dichloro-2-hydroxy-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}formamido)-3-phenylpropanoate dihydrochloride

Smiles: Cl.Cl.CN1CCN(CCOC2=C(Cl)C=C(C(O)=C2Cl)C(=O)N[C@@H](CC2C=CC=CC=2)C(=O)OCC)CC1

InChiKey: JUJAUEQJEWIWCQ-FJSYBICCSA-N

InChi: 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

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: To be determined

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vitro:

JTE-607 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. The inhibitory effects of JTE-607 are also seen in mRNA expression of those cytokines. JTE-607 inhibits inflammatory cytokine production from LPS-stimulated human PBMCs with an IC50 of approximately 10 nM. JTE607 inhibits LPS-stimulated IL-8 production from monkey and rabbit PBMCs, and TNF-α production from mouse and rat PBMCs with IC50s of 59, 780, 1600 and 19000 nM, respectively. JTE607 also suppresses other cytokines, granulocyte-macrophage colony stimulating factor and IL-1RA with IC50s of 2.4±0.8 and 5.4±0.4 nM, respectively. JTE-607 inhibits cytokine production in monkey, rabbit, mouse and rat with IC50s of 59±26, 780±120, 1600±650 and 19000±3200 nM, respectively.

In Vivo:

JTE-607 (0.3-10 mg/kg, i.v.) shows dose dependent inhibition of mortality after LPS challenge in C. parvum sensitized mice in accordance with a decrease of plasma TNF-α.

References:

1. Nathan T Ross, et al. CPSF3-dependent pre-mRNA processing as a druggable node in AML and Ewing's sarcoma. Nat Chem Biol. 2020 Jan;16(1):50-59.
2. M Kakutani, et al. JTE-607, a novel inflammatory cytokine synthesis inhibitor without immunosuppression, protects from endotoxin shock in mice. Inflamm Res. 1999 Aug;48(8):461-8.

Products are for research use only. Not for human use.