CU-CPT-8m

Description: CU-CPT-8m is a potent and specific antagonist of Toll-like receptor 8 (TLR8) with an IC50 of 67 nM. Endosomal Toll-like receptors (TLR3, TLR7, TLR8, and TLR9) are highly analogous sensors for various viral or bacterial RNA and DNA molecular patterns. Nonetheless, few small molecules can selectively modulate these TLRs. CU-CPT-8m is the first human TLR8-specific small-molecule antagonists via a novel inhibition mechanism. Crystal structures of two distinct TLR8-ligand complexes validated a unique binding site on the protein-protein interface of the TLR8 homodimer. Upon binding to this new site, the small-molecule ligands stabilize the preformed TLR8 dimer in its resting state, preventing activation. CU-CPT-8m is able to suppress TLR8-mediated proinflammatory signaling in various cell lines, human primary cells, and patient specimens. These results not only suggest a novel strategy for TLR inhibitor design, but also shed critical mechanistic insight into these clinically important immune receptors.

References: Nat Chem Biol. 2018 Jan; 14(1):58-64.

Related CAS#: 2109805-75-4 (CU-CPT17e); 2165340-32-7 (CU-CPT-9b); 2162962-69-6 (CU-CPT-9a)