2. E6446 dihydrochloride

E6446 dihydrochloride is a potent and orally acitve TLR7 and TLR9 antagonist, used in the research of deleterious inflammatory responses. E6446 dihydrochloride is also a potent SCD1 inhibitor (KD: 4.61 μM), significantly inhibiting adipogenic differentiation and hepatic lipogenesis through SCD1-ATF3 signaling. E6446 dihydrochloride also improves liver pathology in high-fat diet (HFD)-fed mice and may be useful in the study of non-alcoholic fatty liver disease (NAFLD).

For research use only. We do not sell to patients.

E6446 dihydrochloride Chemical Structure

E6446 dihydrochloride Chemical Structure

CAS No. : 1345675-25-3

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Solid + Solvent
10 mM * 1 mL in DMSO
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Based on 1 publication(s) in Google Scholar

Other Forms of E6446 dihydrochloride:

E6446 dihydrochloride Related Antibodies

Top Publications Citing Use of Products

1 Publications Citing Use of MCE E6446 dihydrochloride

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Description

E6446 dihydrochloride is a potent and orally acitve TLR7 and TLR9 antagonist, used in the research of deleterious inflammatory responses. E6446 dihydrochloride is also a potent SCD1 inhibitor (KD: 4.61 μM), significantly inhibiting adipogenic differentiation and hepatic lipogenesis through SCD1-ATF3 signaling. E6446 dihydrochloride also improves liver pathology in high-fat diet (HFD)-fed mice and may be useful in the study of non-alcoholic fatty liver disease (NAFLD)[1][2][3].

IC50 & Target

TLR7, TLR9, SCD1[1]
In Vitro

E6446 dihydrochloride is a potent and orally acitve TLR7 and TLR9 inhibitor. E6446 potently suppresses DNA stimulation of HEK:TLR9 cells, with an IC50 value of 10 nM, but is significantly less effective at suppressing LPS endotoxin stimulation of HEK:TLR4 cells or R848 stimulation of HEK:TLR7 cells. E6446 potently inhibits IL-6 production induced by CpG2216 but is ineffective against induction by the TLR3 ligand poly inosine-cytosine. The ability of E6446 to inhibit TLR7 is ligand dependent, E6446 is a potent inhibitor of IL-6 induction by RNA but a relatively poor inhibitor of IL-6 induction by the small molecule imidazoquinoline ligand R-848. E6446 suppress TLR9-DNA interaction in vitro, with an IC50 in the 1 to 10 μM range[1]. E6446 (0.01-0.03 μM) specifically inhibits TLR9 activation with CpG ODN 2006, and blocks TLR7/8 activated by the imidazoquinoline compound R848 at 2-8 μM. E6446 reduces 50% of TLR4 activation at 30 μM, and shows IC50s of 0.01 μM and 0.23 μM in HEK-TLR9 cells stimulated with oligo 2006 and in human PBMCs stimulated with oligo 2216, respectively[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

E6446 dihydrochloride Related Antibodies
In Vivo

E6446 (20 mg/kg, p.o.) almost cmlpletely inhibits CpG1668-induced IL-6 production, and dose-dependently suppresses the development of ANA (anti-nuclear antibodies) in mice at 20 and 60 mg/kg[1]. E6446 (20, 60 mg/kg, p.o.) dose-dependently inhibits TLR9 signaling in mice. E6446 (60, 120 mg/kg, p.o.) prevents hyperresponsiveness of TLRs and LPS-induced septic shock in rodent malaria, diminishes TLR responsiveness during acute malaria, suppresses activation of both TLR7 and TLR9[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Molecular Weight

522.51

Formula

C27H37Cl2N3O3
CAS No.
Appearance

Solid

Color

White to off-white

SMILES

[H]Cl.[H]Cl.C1(C2=CC=C(OCCCN3CCCC3)C=C2)=NC4=CC=C(OCCCN5CCCC5)C=C4O1
Shipping

Room temperature in continental US; may vary elsewhere.
Storage
Powder -20°C 3 years
4°C 2 years
In solvent -80°C 2 years
-20°C 1 year
Solvent & Solubility
In Vitro: 

DMSO : 7.6 mg/mL (14.55 mM; Need ultrasonic and warming; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

Preparing
Stock Solutions
Concentration Solvent Mass 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
View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

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This equation is commonly abbreviated as: C1V1 = C2V2

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In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:

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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Calculation results:
Working solution concentration: mg/mL
Purity & Documentation

Purity: 99.96%

COA (244 KB) HNMR (150 KB) LCMS (339 KB)

Handling Instructions (2659 KB)
Cell Assay
[1]

E6446 is assayed for the suppression of BALB/c mouse spleen interleukin-6 (IL-6) production in response to stimulation by oligonucleotide CpG1668. E6446 is added to dissociated splenocytes (5 × 105 per well in complete RPMI/10% fetal bovine serum in a 96-well plate) before addition of TLR agonists. Cells are stimulated for 72 hours, and supernatants are removed for ELISA analysis of IL-6. Mouse bone marrow-derived dendritic cells (BMDCs) are generated by culturing BALB/c marrow cells in RPMI containing 100 ng/mL Flt3 ligand for 7 days. Cells (1 × 105) in 50 μL are assayed for IL-6 production after overnight or 24-hour stimulation with various TLR ligands. For studies using human peripheral blood mononuclear cells, Ficoll-separated mononuclear cells are isolated from healthy volunteer donors, washed, and plated with stimulatory oligonucleotide CpG2216 in complete RPMI for 72 hours. Interferon in supernatant is quantified by ELISA[1].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration
[1]

Mice[1]
MRL/lpr mice are dosed orally five times a week with 20 or 60 mg/kg E6446 or 60 mg/kg hydroxychloroquine beginning at 5 weeks of age. Cytoxan is administered at 50 mg/kg i.p. every 10 days. A serum sample is taken immediately before the beginning of treatment to monitor changes in autoreactive antibodies. Subsequently, serum samples are collected approximately monthly and analyzed for anti-dsDNA by ELISA after 1:500 dilution. Body weights and urine samples are taken at the same interval, and proteinuria is assessed by ChemStrips. Anti-nuclear antibodies (ANA) are assessed using commercially available HEp2 slide kits, with serum diluted to 1:100 in kit buffer. ANA scores are read blinded[1].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
DMSO 1 mM 1.9138 mL 9.5692 mL 19.1384 mL 47.8460 mL
5 mM 0.3828 mL 1.9138 mL 3.8277 mL 9.5692 mL
10 mM 0.1914 mL 0.9569 mL 1.9138 mL 4.7846 mL
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Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

E64461345675-25-3E 6446E-6446Inhibitorinhibitorinhibit

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E6446 dihydrochloride
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