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Chemical Structure| 1219925-73-1 Chemical Structure| 1219925-73-1

Structure of E6446
CAS No.: 1219925-73-1

Chemical Structure| 1219925-73-1

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E-6446 is a synthetic antagonist for nucleic acid-sensing TLRs and potently suppresses DNA stimulation of HEK:TLR9 cells with IC50 of 10 nM.

Synonyms: E6446

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Product Details of E6446

CAS No. :1219925-73-1
Formula : C27H35N3O3
M.W : 449.59
SMILES Code : C1(C2=CC=C(OCCCN3CCCC3)C=C2)=NC4=CC=C(OCCCN5CCCC5)C=C4O1
Synonyms :
E6446
MDL No. :MFCD28900679
InChI Key :YMYJXFUPMPMETB-UHFFFAOYSA-N
Pubchem ID :45102599

Safety of E6446

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Related Pathways of E6446

pyroptosis
TLR

Isoform Comparison

Biological Activity

Description
E6446 serves as a potent, orally active antagonist of TLR7 and TLR9, employed in studying harmful inflammatory responses. It is also a strong SCD1 inhibitor (KD: 4.61 μM), markedly reducing adipogenic differentiation and hepatic lipogenesis via SCD1-ATF3 signaling. Furthermore, E6446 ameliorates liver pathology in mice fed a high-fat diet (HFD), suggesting its utility in researching non-alcoholic fatty liver disease (NAFLD)[1][2][3].

In Vitro:

Cell Line
Concentration Treated Time Description References
Mouse spleen cells 0.01–0.1 μM 72 hours E6446 diminished IL-6 production in response to TLR9 agonist PMC3048158
HEK293 cells 0.01–0.03 μM overnight E6446 specifically inhibited TLR9 activation PMC3048158
OP9 cells 10 μM 15 days E6446 significantly inhibited adipogenic differentiation, reduced lipid droplet accumulation, and downregulated the expression of adipocyte differentiation marker genes Pparg, Fasn, Fabp4, and C/ebpα. PMC10544195
AML12 cells 10 μM 48 hours E6446 significantly inhibited hepatic steatosis, reduced lipid droplet accumulation, and downregulated the expression of lipogenesis-related genes C/ebpα, Fasn, and Fabp4. PMC10544195
Cardiomyocytes 10 µM 6 hours E6446 significantly reduced Il6 and Il1b mRNA expression in CCCP-treated cardiomyocytes but had no effect on the number of PicoGreen and LC3B double-positive deposits. PMC6610159
Cardiomyocytes 0 to 10 µM 6 hours E6446 significantly reduced the induction of Il6, Il1b, and Tnfa mRNAs in response to ODN1668 but had no effect on the cytokine mRNAs induced by LPS or loxoribine. PMC6610159
Human peripheral blood mononuclear cells (PBMCs) 0.05 μM 72 hours E6446 diminished IL-6 production in response to TLR9 and TLR8 agonists PMC3048158

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
C57BL/6 mice Experimental cerebral malaria (ECM) model Oral 120 mg/kg Once daily from day −1 to day 12 post-infection E6446 treatment reduced proinflammatory cytokine production and prevented the development of ECM PMC3048158
C57BL/6J mice Pressure overload-induced heart failure model Oral 1.5 mg/200μL Every 2 days for 4 weeks E6446 significantly attenuated TAC-induced left ventricular dilatation and cardiac dysfunction, reduced cardiac fibrosis and inflammatory responses. PMC6610159
C57BL/6J mice High-fat diet-induced nonalcoholic fatty liver disease model Oral gavage 20 mg/kg Three times per week for 6 weeks E6446 significantly alleviated high-fat diet-induced hepatic steatosis, hepatic lipid droplet accumulation, and insulin resistance. PMC10544195
Sprague-Dawley rats Monocrotaline-induced pulmonary hypertension model Oral administration in drinking water 10 mg/kg From 3 days before to 21 days after monocrotaline injection To evaluate the preventive and therapeutic effects of TLR9 inhibitors on pulmonary hypertension, results showed that E6446 significantly improved hemodynamic parameters, vascular remodeling, and survival in pulmonary hypertension PMC8174358

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.22mL

0.44mL

0.22mL

11.12mL

2.22mL

1.11mL

22.24mL

4.45mL

2.22mL

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1

References

 

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