CU-CPT-9b

Description: CU-CPT-9b, an analog of CU-CPT-8m and CU-CPT-9a, is a potent and specific antagonist of TLR8 (Toll-like receptor 8) with IC50 of 0.7 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. ITC experiments have confirmed the strong binding of CU-CPT-9b with a Kdof 21 nM. It is shown that CU-CPT-9b binds to the inactive TLR8 dimer in a similar way to CU-CPT8m. CU-CPT9b utilizes hydrogen bonds with G351 and V520*, which are conserved among TLR8/antagonist structures. Additionally, CU-CPT-9b forms water-mediated contacts with S516* and Q519*, which are not observed in TLR8/CU-CPT8m structure, suggesting that the enhanced potency of CU-CPT-9b derives from the new interactions with these polar residues. The orientation of Y567* also changes to facilitate van der Waals interactions with CU-CPT-9b as compared to TLR8/CU-CPT8m.

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

Related CAS#: 2162962-69-6 (CU-CPT-9b); 2109805-75-4 (CU-CPT17e); 125079-83-6 (CU-CPT-8m); 2165340-32-7 (CU-CPT-9a)