| Size | Price | Stock | Qty |
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| 10mg |
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| 25mg |
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| Targets |
JTE-607 HCl is a high-selectivity inhibitor of inflammatory cytokine synthesis. It targets the production of multiple pro-inflammatory cytokines, including TNF-α, IL-1β, IL-6, and IL-8, as well as the anti-inflammatory cytokine IL-10. The exact molecular target is not detailed in the provided search results, but its mechanism involves inhibition of cytokine synthesis without immunosuppression. It also induces apoptosis in acute myelogenous leukemia cells.
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| ln Vitro |
JTE-607, with an IC50 of 11, 5.9, 8.8, 7.3, and 9.1 nM, respectively, suppresses the production of inflammatory cytokines by LPS-stimulated human PBMC, including TNF-α, IL-1β, IL-6, IL-8, and IL-10. JTE-607 also has an inhibitory effect on these cytokines' mRNA expression [1]. With an IC 50 of roughly 10 nM, JTE-607 suppresses the release of inflammatory cytokines by LPS-stimulated human PBMC [1]. JTE607 has an IC50 of 59, 780, 1600, and 19000 nM, respectively, which suppresses the production of TNF-α in mouse and rat PBMC and LPS-stimulated IL-8 in monkey and rabbit PBMC [1]. Moreover, JTE607 suppresses IL-1RA and granulocyte-macrophage colony-stimulating factor, with IC50 values of 5.4±0.4 nM and 2.4±0.8 nM, respectively[1]. In monkey, rabbit, mouse, and rat, JTE-607 suppresses cytokine production with IC50 values of 59±26, 780±120, 1600±650, and 19000±3200 nM, respectively[1].
In vitro, JTE-607 HCl is a potent inhibitor of inflammatory cytokine production. It inhibits LPS-stimulated production of TNF-α, IL-1β, IL-6, IL-8, and IL-10 in human PBMCs with IC50s of 11, 5.9, 8.8, 7.3, and 9.1 nM, respectively. It induces apoptosis accompanied by an increase in p21waf1/cip1 in acute myelogenous leukemia cells. Its activity is characterized by its ability to inhibit multiple cytokine pathways. |
| ln Vivo |
After an LPS exposure in C, JTE-607 (0.3–10 mg/kg, iv) dose-dependently lowers mortality. mice susceptible to parvum, while lowering TNF-α in mouse plasma [1].
In vivo, JTE-607 HCl protects mice from endotoxin shock. This demonstrates its efficacy in a model of systemic inflammation. Its ability to inhibit inflammatory cytokine production without immunosuppression makes it a potential therapeutic agent for systemic inflammatory response syndrome and other inflammatory conditions. Further studies are needed to fully characterize its in vivo efficacy and safety. |
| Enzyme Assay |
The in vitro activity of JTE-607 HCl is assessed using cell-based cytokine production assays. Human peripheral blood mononuclear cells (PBMCs) are isolated and stimulated with LPS in the presence of varying concentrations of JTE-607 HCl. The levels of cytokines (TNF-α, IL-1β, IL-6, IL-8, IL-10) in the culture medium are measured by ELISA. The IC50 is determined from dose-response curves. For apoptosis studies, acute myelogenous leukemia cells are treated with JTE-607 HCl.
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| Cell Assay |
RT-PCR[1]
Cell Types: human peripheral blood mononuclear cells (PBMCs) Tested Concentrations: 100 nM Incubation Duration: 20 hrs (hours) Experimental Results: decreased the increase in the level of mRNAs of TNF-α, IL-1b, IL-6 and IL -8. For cellular assays, human PBMCs or acute myelogenous leukemia cell lines are cultured in appropriate media. Cells are treated with various concentrations of JTE-607 HCl (typically 0.1-1000 nM) for defined periods. Cytokine levels are measured by ELISA. Apoptosis is evaluated by flow cytometry using Annexin V/PI staining or by measuring caspase-3/7 activity. The expression of p21waf1/cip1 is analyzed by Western blotting. Cell viability is assessed using standard assays. |
| Animal Protocol |
Animal/Disease Models: Male C57BL/6 mice (5 to 6 weeks old) are sensitized by injecting Corynebacterium parvum[1]
Doses: 0.3, 1, 3, 10 mg/kg Route of Administration: Administered intravenously (iv)10 min before the LPS challenge. Experimental Results: demonstrated dose dependent inhibition of the mortality at 0.3 to 10 mg/kg and significant effect at 3 and 10 mg/kg. In vivo, JTE-607 HCl is typically administered intraperitoneally or intravenously to animal models of endotoxin shock. The compound is formulated in a suitable vehicle and administered at various doses. Efficacy is assessed by measuring survival, cytokine levels in plasma, and markers of inflammation. Pharmacokinetic studies involve measuring JTE-607 HCl levels in plasma. Toxicological studies are performed to assess the compound's safety profile. |
| ADME/Pharmacokinetics |
JTE-607 HCl has a molecular weight of approximately 597.36 g/mol (dihydrochloride salt) and a molecular formula of C25H33Cl3N3O5. It is a pro-drug that is cleaved to its active form. The compound should be stored under appropriate conditions as recommended by the manufacturer. Specific solubility and pharmacokinetic parameters are not detailed in the provided search results.
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| Toxicity/Toxicokinetics |
Specific toxicity data for JTE-607 HCl is not available in the provided search results. As a cytokine production inhibitor, it may affect the immune system and potentially increase susceptibility to infections. The compound is intended for research purposes only and is not approved for human or veterinary use. Standard laboratory safety precautions should be followed when handling the compound. Comprehensive toxicological studies are required to establish its full safety profile.
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| References | |
| Additional Infomation |
JTE-607 dihydrochloride is the dihydrochloride of JTE-607. It is a cytokine inhibitor that inhibits the production of pro-inflammatory cytokines such as interleukin-1β (IL-1β), IL-6, IL-8, granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor-α (TNF-α). As a prodrug, it is cleaved by carboxylesterase 1 (CES1) into its active free acid form, and then bound to cleavage and polyadenylation-specific factor 3 (CPSF3). It possesses multiple effects, including anti-inflammatory, anti-tumor, apoptosis-inducing, prodrug-based, cardioprotective, and CPSF3 inhibitory properties. It contains JTE-607(2+).
JTE-607 HCl is a potent inhibitor of inflammatory cytokine production. It inhibits the production of TNF-α, IL-1β, IL-6, IL-8, and IL-10 in LPS-stimulated human PBMCs with IC50s in the nanomolar range. It protects mice from endotoxin shock and induces apoptosis in acute myelogenous leukemia cells. JTE-607 HCl is a valuable research tool for studying inflammation and cytokine signaling. The compound is not approved for clinical use and is intended for research purposes only. |
| Molecular Formula |
C22H29CL4N3O3
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|---|---|
| Molecular Weight |
525.292
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| Exact Mass |
595.117
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| Elemental Analysis |
C, 50.27; H, 5.57; Cl, 23.74; N, 7.03; O, 13.39
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| CAS # |
188791-09-5
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| Related CAS # |
188791-71-1;188791-09-5 (HCl);
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| PubChem CID |
9938544
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| Appearance |
White to off-white solid powder
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| LogP |
5.284
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
11
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| Heavy Atom Count |
37
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| Complexity |
674
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| Defined Atom Stereocenter Count |
1
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| SMILES |
ClC1=C(C(C(N([H])[C@]([H])(C(=O)OC([H])([H])C([H])([H])[H])C([H])([H])C2C([H])=C([H])C([H])=C([H])C=2[H])=O)=C([H])C(=C1OC([H])([H])C([H])([H])N1C([H])([H])C([H])([H])N(C([H])([H])[H])C([H])([H])C1([H])[H])Cl)O[H].Cl[H].Cl[H]
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| InChi Key |
JUJAUEQJEWIWCQ-FJSYBICCSA-N
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| 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
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| Chemical Name |
N-[3,5-Dichloro-2-hydroxy-4-[2-(4-methyl-1-piperazinyl)ethoxy]benzoyl]-L-phenylalanine ethyl ester dihydrochloride
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| Synonyms |
TO-207; TO 207; TO207; JTE-607; JTE 607; JTE 607; JTE-607 HCl; JTE-607 dihydrochloride.
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~250 mg/mL (~418.51 mM)
H2O : ~20 mg/mL (~33.48 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (3.48 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (3.48 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (3.48 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 100 mg/mL (167.40 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9037 mL | 9.5186 mL | 19.0371 mL | |
| 5 mM | 0.3807 mL | 1.9037 mL | 3.8074 mL | |
| 10 mM | 0.1904 mL | 0.9519 mL | 1.9037 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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