TLR8 Antagonist

TLR8 antagonist-2 (Compound 35) is a selective TLR8 antagonist with an IC₅₀ of 0.032 μM against hTLR8. TLR8 antagonist-2 potently inhibits TLR8-dependent NF-κB activity in cells stimulated with TL8-506 (HY-20457). TLR8 antagonist-2 can be used in research related to inflammatory and immune diseases.

CU-CPT-9a is a specific TLR8 antagonist, with an IC₅₀ of 0.5 nM.

CU-CPT-8m is a specific TLR8 antagonist, with an IC₅₀ of 67 nM.

CU-115 is a potent TLR8 antagonist (IC₅₀=1.04 µM), and shows selective for TLR8 over TLR7 (IC₅₀=>50 µM). CU-115 decreases TNF-α and IL-1β production activated by R-848 in THP-1 cells.

CU-CPT9b is a specific TLR8 antagonist, with an IC₅₀ of 0.7 nM. CU-CPT9b shows high binding affinity towards TLR8 with a K_d of 21 nM.

TLR9 antagonist 1 is a selective hTLR9 antagonist with an IC₅₀ of 0.1 nM against hTLR9. TLR9 antagonist 1 exhibits favorable pharmacokinetic and pharmacodynamic properties. TLR9 antagonist 1 can be used in the research of systemic lupus erythematosus.

SMU-R39 is a TLR7 and TLR8 antagonist with IC₅₀ values of 3.22 μM and 0.24 μM, respectively. SMU-R39 binds to recombinant mTLR7 protein (K_D = 2.36 μM) and to recombinant hTLR8 protein (K_D = 105 nM). SMU-R39 suppresses downstream NF-κB and MAPK signaling, and reduces secretion/transcription of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) in PBMCs and THP-1 cells. SMU-R39 demonstrates anti-inflammatory efficacy in Imiquimod (IMQ) (HY-B0180)-induced psoriasis mouse model. SMU-R39 can be used for the study of autoimmune diseases such as psoriasis.

TLR7/8 antagonist 1 (Compound 16c) is a competitive TLR7/8 antagonist with IC₅₀ values of 3.91 μM and 2.19 μM, respectively. TLR7/8 antagonist 1 reduces agonist-induced production of proinflammatory cytokines, including TNFα, IFNγ and IL-1β.