6V9U

Crystal structure of human TLR8 ectodomain bound to small molecule antagonist 14c

6V9U の概要

• エントリーDOI: 10.2210/pdb6v9u/pdb
• 分子名称: Toll-like receptor 8, alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (8 entities in total)
• 機能のキーワード: toll-like receptor, pattern recognition receptor, pathogen-associated molecular patterns, innate immunity, endosomal receptor, rna binding protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 194842.52

構造登録者

Critton, D.A. (登録日: 2019-12-16, 公開日: 2020-08-12, 最終更新日: 2024-10-23)

主引用文献

Mussari, C.P.,Dodd, D.S.,Sreekantha, R.K.,Pasunoori, L.,Wan, H.,Posy, S.L.,Critton, D.,Ruepp, S.,Subramanian, M.,Watson, A.,Davies, P.,Schieven, G.L.,Salter-Cid, L.M.,Srivastava, R.,Tagore, D.M.,Dudhgaonkar, S.,Poss, M.A.,Carter, P.H.,Dyckman, A.J.
Discovery of Potent and Orally Bioavailable Small Molecule Antagonists of Toll-like Receptors 7/8/9 (TLR7/8/9).
Acs Med.Chem.Lett., 11:1751-1758, 2020

PubMed Abstract: The toll-like receptor (TLR) family is an evolutionarily conserved component of the innate immune system, responsible for the early detection of foreign or endogenous threat signals. In the context of autoimmunity, the unintended recognition of self-motifs as foreign promotes initiation or propagation of disease. Overactivation of TLR7 and TLR9 have been implicated as factors contributing to autoimmune disorders such as psoriasis, arthritis, and lupus. In our search for small molecule antagonists of TLR7/9, was identified as possessing excellent on-target potency for human TLR7/9 as well as for TLR8, with selectivity against other representative TLR family members. Good pharmacokinetic properties and a relatively balanced potency against TLR7 and TLR9 in mouse systems (systems which lack functional TLR8) made this an excellent in vivo tool compound, and efficacy from oral dosing in preclinical models of autoimmune disease was demonstrated.

PubMed: 32944143
DOI: 10.1021/acsmedchemlett.0c00264

実験手法

X-RAY DIFFRACTION (2.65 Å)