ETI41
ETI41 is an orally active, selective TLR inhibitor that targets the nucleoside-binding Site I on TLR7 (IC50 = 0.63 μM) and TLR9 (IC50 = 0.16 μM), sparing surface TLRs (including TLR1/TLR2, TLR2/TLR6, TLR4 and TLR5). ETI41 potently inhibits endosomal TLR-mediated pro-inflammatory signaling with nanomolar activity in cellular, biophysical and in vivo assays. ETI41 suppresses the expression of inflammation-associated genes and effectively ameliorates symptoms in mouse models of psoriasis, and systemic lupus erythematosus (SLE). ETI41 can be used for autoimmune and inflammatory diseases research.
For research use only. We do not sell to patients.
- CAS No.: 2773474-99-8
- Formula: C19H30N4
- Molecular Weight:314.47
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
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TLR9 0.16 μM (IC50) |
TLR7 0.63 μM (IC50) |
ETI41 (0-200 μM, 4-24 h) effectively inhibits TLR agonist (e.g., Imiquimod (IMQ) (HY-B0180) for TLR7, ODN2395 (HY-150743) for TLR9)-induced TNF-α production in mouse macrophages (RAW 264.7) and human B lymphoblasts (Daudi) cell lines in a dose-dependent manner, without inducing cytotoxic effects[1].
ETI41 (24 h) exhibits inhibitory activity against endosomal TLRs with IC50 values ranging from approximately 100 to 1,000 nM, and inhibits TLR3, TLR7 and TLR8 in a concentration-dependent manner (from 31.2 nM to 10 μM)[1].
ETI41 (5-10 μM, 20 min-8 h) inhibits IMQ- or ODN2395-induced phosphorylation of MAPKs (p-ERK, p-JNK and p-p38), nuclear translocation of the NF-κB p65 subunit, Iκ-Bα degradation and IRF7 expression in RAW 264.7 cells[1].
ETI41 (0.2-1 μM, 30 min) significantly inhibits the production of IL-12p40, IFN-β and CD40 in primary Bone Marrow-derived Dendritic Cells (BMDCs) stimulated with ODN2395[1].
ETI41 (10 μM, 2-4 h) attenuates the IMQ-induced upregulation of multiple inflammation-related genes, including IL1-β, CXCL2, IL18RAP, TNF, PDCD1, NLRP3, NFKBIZ, CCL3, CCL4, KDM6B, ZC3H12A, and PTGS2[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:murine RAW 264.7 and human Daudi cells
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Concentration:1.6-200 μM
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Incubation Time:24 h
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Result:Exhibited no cytotoxicity in both murine RAW 264.7 and human Daudi cells at concentrations up to 10 μM.
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Cell Line:RAW 264.7 cells
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Concentration:5 and 10 μM
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Incubation Time:20, 30, 40, and 50 min, 6 and 8 h
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Result:Reduced p-ERK, p-JNK and p-p38 levels.
Suppressed the nuclear translocation of the NF-κB p65 subunit.
Downregulated IRF7 expression and prevented the degradation of Iκ-Bα.
ETI41 (60 mg/kg, p.o., daily from day 2 to day 9) ameliorates psoriasis induced by IL-23 in mice[1].
ETI41 (30 mg/kg, p.o., daily for 39 days) effectively ameliorates symptoms in a mouse model of SLE[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Female C57BL/6J mice (6 weeks old) induced with psoriasis via intradermal injection of recombinant murine IL-23 (500 ng) around the ear daily for 8 days[1]
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Dosage:60 mg/kg
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Administration:p.o., daily from day 2 to day 9
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Result:Improved disease symptoms comparable to or superior to the positive control (anti-IL-17A antibody, 30 mg/kg, i.p., dose on day 2, 5, and 8), without significant differences in body weight.
Significantly decreased ear and epidermal thicknesses, CD68 expression and Ki-67 keratinocyte proliferation.
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Animal Model:Female C57BL/6J mice (6 weeks old) induced with psoriasis via daily topical application of Aldara cream (IMQ, 62.5 mg/cm²) for 4 days post-shaving[1]
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Dosage:60 mg/kg
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Administration:p.o., daily from day 2 to day 5
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Result:Significantly reduced the Psoriasis Area and Severity Index (PASI) scores, epidermal acanthosis, dermal thickness and keratinocyte proliferation.
Inhibited IL-17A and IL-23 expression and dermal inflammatory cell infiltration.
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Animal Model:Female MRL/MpJ-Faslpr/J lupus-prone mice (14 weeks old)[1]
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Dosage:30 mg/kg
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Administration:p.o., daily for 39 days
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Result:Prevented weight gain or loss and decreased lymphnode weights.
Reduced alopecia and skin rashes compared with the vehicle and HCQ (60 mg/kg, P.O., daily for 39 days).
Reduced serological markers associated with SLE, such as antinuclear antibody (ANA), anti-dsDNA antibodies and IgG in the kidney, compared to HCQ group.
Demonstrated significant reduction in SLE symptoms at half the dose of HCQ, suggesting high efficacy.
Chemical Information
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CAS No. 2773474-99-8
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Molecular Weight 314.47
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Formula C19H30N4
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SMILES
CC(N1CCCN(C)C)=CC(C1=N2)=C(N)C3=C2CCCCCC3
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
ETI41 Related Classifications
HY-178166 Related Classifications
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