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| 2mg |
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| 25mg |
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Purity: ≥98%
E6446 is a synthetic antagonist of nucleic acid-sensing TLRs. , In vitro, low doses of E6446 specifically inhibited the activation of human and mouse TLR9. Tenfold higher concentrations of this compound also inhibited the human TLR8 response to single-stranded RNA. In vivo, therapy with E6446 diminished the activation of TLR9 and prevented the exacerbated cytokine response observed during acute Plasmodium infection. Furthermore, severe signs of ECM, such as limb paralysis, brain vascular leak, and death, were all prevented by orally bioavailable treatment with E6446.
| ln Vitro |
Wall-active TLR7 and TLR9 with strong potency is E6446 dihydrochloride. DNA stimulation of HEK:TLR9 cells is effectively inhibited by E6446 dihydrochloride (IC50 of 10 nM); however, LPS endotoxin stimulation of HEK:TLR4 cells and R848 stimulation of HEK:TLR7 cells are substantially more effectively inhibited. While TLR3 ligand polyinosine-cell cycle factors are not efficiently inhibited by E6446 dihydrochloride, it is effective in blocking IL-6 production triggered by CpG2216. The ligand-coupled mechanism of action of E6446 dihydrochloride efficiently inhibits TLR7. When it comes to RNA-induced IL-6, E6446 dihydrochloride works well. With an IC50 ranging from 1 to 10 μM, E6446 dihydrochloride inhibits TLR9-DNA coupling in vitro. inside the bounds of [1]. When suspended with CpG ODN 2006, dihydrochloride (0.01-0.03 μM) suppresses TLR9 activation and swells TLR7/8 when triggered by the imidazoline chemical R848 at 2-8 μM. When oligo 2006 is used to stimulate HEK-TLR9 cells, and oligo 2216 is used to stimulate human PBMC, E6446 dihydrochloride lowers TLR4 activation by 50% at 30 μM and exhibits an IC50 of 0.01 μM and 0.23 μM, respectively [2].
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| ln Vivo |
E6446 dihydrochloride (20 mg/kg, orally administered) reduces the production of IL-6 produced by CpG1668 nearly entirely and dose-dependently inhibits the generation of ANA (antinuclear antibodies) in mice at 20 and 60 mg/kg [1]. In mice, E6446 dihydrochloride (20, 60 mg/kg, po) suppresses TLR9 signaling in a dose-dependent manner. Oral E6446 dihydrochloride (60, 120 mg/kg) inhibits the activation of TLR7 and TLR9, decreases TLR reactivity during acute malaria, and protects LPS-induced septic shock and TLR hyperresponsiveness in rodent malaria [2].
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| References |
[1]. Lamphier M, et al. Novel small molecule inhibitors of TLR7 and TLR9: mechanism of action and efficacy in vivo. Mol Pharmacol. 2014 Mar;85(3):429-40.
[2]. Franklin BS, et al. Therapeutical targeting of nucleic acid-sensing Toll-like receptors prevents experimental cerebral malaria. Proc Natl Acad Sci U S A. 2011 Mar 1;108(9):3689-94. [3]. Wang W, et al. Identification of novel SCD1 inhibitor alleviates nonalcoholic fatty liver disease: critical role of liver-adipose axis. Cell Commun Signal. 2023 Sep 30;21(1):268 |
| Molecular Formula |
C27H37CL2N3O3
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|---|---|
| Molecular Weight |
522.511
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| CAS # |
1345675-25-3
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| Related CAS # |
E6446;1219925-73-1
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| SMILES |
InChI=1S/C27H35N3O3.2ClH/c1-2-14-29(13-1)17-5-19-31-23-9-7-22(8-10-23)27-28-25-12-11-24(21-26(25)33-27)32-20-6-18-30-15-3-4-16-30/h7-12,21H,1-6,13-20H22*1H
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| InChi Key |
6-(3-pyrrolidin-1-ylpropoxy)-2-[4-(3-pyrrolidin-1-ylpropoxy)phenyl]-1,3-benzoxazoledihydrochloride
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| InChi Code |
DQOUZINBHKWGGM-UHFFFAOYSA-N
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| Chemical Name |
E6446 HCl E6446 E-6446 E6446 hydrochloride
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| 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 : ~7.6 mg/mL (~14.55 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9138 mL | 9.5692 mL | 19.1384 mL | |
| 5 mM | 0.3828 mL | 1.9138 mL | 3.8277 mL | |
| 10 mM | 0.1914 mL | 0.9569 mL | 1.9138 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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