E6446 dihydrochloride

Name: E6446 dihydrochloride
Brand: MedChemExpress
SKU: HY-12756A
Rating: 5.0 (9 reviews)

Cat. No.: HY-12756A Purity: 99.29%: Data Sheet
COA

SDS
Handling Instructions
FAQs
Technical Support

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

CAS No. : 1345675-25-3

Size	Stock	Quantity
Solid + Solvent (Highly Recommended)
10 mM * 1 mL in Water ready for reconstitution	In-stock	Estimated Time of Arrival: December 31
Solution
10 mM * 1 mL in Water	In-stock	Estimated Time of Arrival: December 31
Solid
5 mg	In-stock	Estimated Time of Arrival: December 31
10 mg	In-stock	Estimated Time of Arrival: December 31
25 mg	In-stock	Estimated Time of Arrival: December 31
50 mg	In-stock	Estimated Time of Arrival: December 31
100 mg	In-stock	Estimated Time of Arrival: December 31
200 mg	Get quote
500 mg	Get quote

or Bulk Inquiry

* Please select Quantity before adding items.

This product is a controlled substance and not for sale in your territory.

Customer Review

Based on 9 publication(s) in Google Scholar

Other Forms of E6446 dihydrochloride:

E6446 In-stock
E6446 dihydrochloride (Standard) Get quote

9 Publications Citing Use of MCE E6446 dihydrochloride

Featured Recommendations

•Related Screening Libraries:

•Related Small Molecules:

•Related Proteins:

View All Toll-like Receptor (TLR) Isoform Specific Products:

View All Isoforms

TLR3 TLR8 TLR9 TLR2 TLR4 TLR7 TLR1 TLR6

Biological Activity
Protocol
Purity & Documentation
References
Customer Review

Description

IC₅₀ & Target^[1]^[3]

TLR7

TLR9

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.

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.

1345675-25-3

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:

H₂O : ≥ 100 mg/mL (191.38 mM)

DMSO : 5 mg/mL (9.57 mM; ultrasonic and warming and heat to 60°C; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

*"≥" means soluble, but saturation unknown.

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
10 mM	0.1914 mL	0.9569 mL	1.9138 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.

* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.

Molarity Calculator
Dilution Calculator

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Concentration _(start) × Volume _(start) = Concentration _(final) × Volume _(final)

This equation is commonly abbreviated as: C₁V₁ = C₂V₂

Concentration _(start)

Volume _(start)

Concentration _(final)

Volume _(final)

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

Dosage

mg/kg

Animal weight
(per animal)

Dosing volume
(per animal)

μL

Number of animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Calculation results:

Working solution concentration: mg/mL

This product has good water solubility, please refer to the measured solubility data in water/PBS/Saline for details.

The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only.If necessary, please contact MedChemExpress (MCE).

Purity & Documentation

Purity: 99.29%

Select Batch:

Data Sheet (276 KB) SDS (393 KB)

COA (244 KB) HNMR (179 KB) LCMS (96 KB)

Handling Instructions (2659 KB)

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. [Content Brief]

[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. [Content Brief]

[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. [Content Brief]

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.
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. [Content Brief] [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. [Content Brief] [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. [Content Brief]

Complete Stock Solution Preparation Table

Optional Solvent	Concentration Solvent Mass	1 mg	5 mg	10 mg	25 mg

DMSO / H₂O	1 mM	1.9138 mL	9.5692 mL	19.1384 mL	47.8460 mL
DMSO / H₂O	5 mM	0.3828 mL	1.9138 mL	3.8277 mL	9.5692 mL
H₂O	10 mM	0.1914 mL	0.9569 mL	1.9138 mL	4.7846 mL
	15 mM	0.1276 mL	0.6379 mL	1.2759 mL	3.1897 mL
	20 mM	0.0957 mL	0.4785 mL	0.9569 mL	2.3923 mL
	25 mM	0.0766 mL	0.3828 mL	0.7655 mL	1.9138 mL
	30 mM	0.0638 mL	0.3190 mL	0.6379 mL	1.5949 mL
	40 mM	0.0478 mL	0.2392 mL	0.4785 mL	1.1961 mL
	50 mM	0.0383 mL	0.1914 mL	0.3828 mL	0.9569 mL
	60 mM	0.0319 mL	0.1595 mL	0.3190 mL	0.7974 mL
	80 mM	0.0239 mL	0.1196 mL	0.2392 mL	0.5981 mL
	100 mM	0.0191 mL	0.0957 mL	0.1914 mL	0.4785 mL

* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.