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Submit ReviewJTE 607 dihydrochloride
Description: Active metabolite binds CPSF3; Pro-drug
Alternative Names: TO-207
Chemical Name: N-[3,5-Dichloro-2-hydroxy-4-[2-(4-methyl-1-piperazinyl)ethoxy]benzoyl]-L-phenylalanine ethyl ester dihydrochloride
Purity: ≥98% (HPLC)
Biological Activity for JTE 607 dihydrochloride
JTE 607 dihydrochloride is a JTE 607 is a pro-drug that is cleaved by carboxylesterase 1 (CES1) to its active metabolite, which then binds to cleavage and polyadenylation specificity factor 3 (CPSF3; Kd = 370 nM at human CPSF3). Treatment of A-673 cells with JTE 607 results in inhibition of mRNA cleavage and accumulation of nuclear R-loops. JTE 607 induces apoptosis in leukemia cells in vitro and prolongs survival in a mouse leukemia model.
JTE 607 also inhibits cytokine release; it inhibits production of IL-1β, IL-8, IL-6, IL-10 and TNFα (IC50 values are 5.9, 7.3, 8.8, 9.1 and 11.0 nM, respectively) from LPS-stimulated PBMCs. In a rat model of lung injury, JTE 607 reduces proinflammatory cytokine-release and attenuates lung permeability.
Compound Libraries for JTE 607 dihydrochloride
JTE 607 dihydrochloride is also offered as part of the Tocriscreen 2.0 Max and Tocriscreen Antiviral Library. Find out more about compound libraries available from Tocris.
Technical Data for JTE 607 dihydrochloride
| M. Wt | 597.36 |
| Formula | C25H31Cl2N3O5.2HCl |
| Storage | Desiccate at RT |
| Purity | ≥98% (HPLC) |
| CAS Number | 188791-09-5 |
| PubChem ID | 9938544 |
| InChI Key | JUJAUEQJEWIWCQ-FJSYBICCSA-N |
| Smiles | ClC1=C(OCCN2CCN(C)CC2)C(Cl)=CC(C(N[C@@H](CC3=CC=CC=C3)C(OCC)=O)=O)=C1O.Cl.Cl |
The technical data provided above is for guidance only. For batch specific data refer to the Certificate of Analysis.
Tocris products are intended for laboratory research use only, unless stated otherwise.
Solubility Data for JTE 607 dihydrochloride
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| water | 59.74 | 100 | |
| DMSO | 59.74 | 100 |
Preparing Stock Solutions for JTE 607 dihydrochloride
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 | 1.67 mL | 8.37 mL | 16.74 mL |
| 5 mM | 0.33 mL | 1.67 mL | 3.35 mL |
| 10 mM | 0.17 mL | 0.84 mL | 1.67 mL |
| 50 mM | 0.03 mL | 0.17 mL | 0.33 mL |
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Product Datasheets for JTE 607 dihydrochloride
References for JTE 607 dihydrochloride
References are publications that support the biological activity of the product.
Kakutani et al (1999) JTE-607, a novel inflammatory cytokine synthesis inhibitor without immunosuppression, protects from endotoxin shock in mice. Inflamm.Res. 48 461 PMID: 10493164
Jian (2004) JTE-607, a cytokine release blocker, attenuates acid aspiration-induced lung injury in rats. Eur.J.Pharmacol. 488 231 PMID: 15044056
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 PMID: 20028380
Ross et al (2020) CPSF3-dependent pre-mRNA processing as a druggable node in AML and Ewing's sarcoma. Nat.Chem.Biol. 16 50 PMID: 31819276
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1 Citation for JTE 607 dihydrochloride
Citations are publications that use Tocris products. Selected citations for JTE 607 dihydrochloride include:
Futami et al (2020) The novel multi-cytokine inhibitor TO-207 specifically inhibits pro-inflammatory cytokine secretion in monocytes without affecting the killing ability of CAR T cells PLoS One 15 PMID: 32320454
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