E6446 dihydrochloride

SKU: orb1303204

Description

E6446 dihydrochloride is a potent and selective synthetic antagonist of nucleic acid-sensing Toll-like receptors (TLRs). It inhibits DNA-induced TLR9 signaling in HEK293 cells with an IC50 of 10 nM, making it a valuable tool for studying innate immune pathways in vitro and in vivo models of autoimmune and inflammatory diseases.

Research Area

Immunology & Inflammation, Metabolism Research

Key Properties

• CAS Number: 1345675-25-3
• MW: 522.51
• Purity: 99.44%
• Formula: C₂₇H₃₇Cl₂N₃O₃
• SMILES: Cl.Cl.C(COc1ccc(cc1)-c1nc2ccc(OCCCN3CCCC3)cc2o1)CN1CCCC1
• Target: TLR,Stearoyl-CoA Desaturase (SCD)
• Solubility: DMSO:5.23 mg/mL (10.01 mM)

Bioactivity

• Target IC50:
  TLR9:10 nM.
• In Vivo:
  To test their activity in vivo, mice were orally dosed with 20 mg/kg of AT791 or E6446 and 18 hours later were challenged with 60 μg CpG1668 oligonucleotide injected subcutaneously. CpG1668-induced IL-6 production was inhibited ~50% by AT791 and almost completely by E6446 . therapy with E6446 diminished the activation of TLR9 and prevented the exacerbated cytokine response observed during acute Plasmodium infection .
• In Vitro:
  E6446 potently inhibited IL-6 production induced by CpG2216 but was ineffective against induction by the TLR3 ligand poly inosine-cytosine. E6446 showed a modest but consistent superiority over AT791, and both were significantly more potent than hydroxychloroquine. Significantly, 250 nM and 1.25 μM E6446 completely suppressed all of the CpG oligo-induced changes in gene expression . E6446 specifically inhibited TLR9 activation with CpG ODN 2006, in the range of 0.01–0.03 μM. A 100-fold higher concentration (2–8 μM) of E6446 was required to inhibit TLR7/8 activated by the imidazoquinoline compound R848 .

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

E6446, E-6446, E6446 dihydrochloride, E6446 Dihydrochloride, E-6446 Dihydrochloride, E-6446 dihydrochloride, E 6446, E 6446 Dihydrochloride, TLR

Compound Identifiers

PubChem CID

72698607