Neuropore Therapies Inc., 10835 Road to the Cure, Suite 230, San Diego, CA 92121, USA.
MolSoft LLC., 11199 Sorrento Valley Rd # 209, San Diego, CA 92121, USA.
Bioorg Med Chem Lett. 2021 May 15;40:127861. doi: 10.1016/j.bmcl.2021.127861. Epub 2021 Feb 23.
Toll-like receptors (TLRs) play key role in innate immune response to Damage Associated Molecular Patterns (DAMPs) and Pathogen Associated Molecular Patterns (PAMPs). DAMP/PAMP-mediated activation of TLRs triggers NFκB signaling resulting in pro-inflammatory cytokine release. Using TLR2-Pam2CSK4 agonist co-crystal structure information, we designed and synthesized a novel series of Toll-like Receptor 2 (TLR2) lipid antagonists and identified compounds 14, 15 and 17 with sub-micromolar potency. TLR2 antagonists that we identified are stable for > 1.0 h in both gastric juice and PBS buffer and could be used as research tools.
Toll 样受体 (TLRs) 在先天免疫对损伤相关分子模式 (DAMPs) 和病原体相关分子模式 (PAMPs) 的反应中发挥关键作用。DAMP/PAMP 介导的 TLR 激活触发 NFκB 信号传导，导致促炎细胞因子的释放。利用 TLR2-Pam2CSK4 激动剂共晶结构信息，我们设计并合成了一系列新型 Toll 样受体 2 (TLR2) 脂质拮抗剂，并鉴定出化合物 14、15 和 17 具有亚微摩尔的效力。我们鉴定出的 TLR2 拮抗剂在胃液和 PBS 缓冲液中均稳定超过 1.0 小时，可作为研究工具使用。
