FPS-ZM1 is a high-affinity RAGE specific inhibitor that blocks Aβ binding to the V domain of RAGE.

RAGE:25 nM. (Ki)

FPS-ZM1通过阻断Aβ与RAGE的V区域的结合，抑制了体外表达RAGE细胞中Aβ40和Aβ42引起的细胞应激。它还能阻断其他配体（如S100B、AGE、HMGB1）与RAGE的结合，这些配体被认为在糖尿病、免疫/炎症性疾病以及阿尔茨海默病（AD）[1]模型中通过RAGE介导长期组织损伤的过程中发挥作用。

FPS-ZM1对小鼠无毒且能轻松穿过血脑屏障(BBB)。在完全发展了Aβ和淀粉样病理的17月龄APPsw/0小鼠中，通过阻断BBB和大脑中的RAGE作用，有效控制了Aβ介导的脑部疾病进程及相关神经血管和认知功能障碍。此外，FPS-ZM1在17月龄APPsw/0小鼠的大脑中阻断了依赖RAGE的BACE1表达和活性[1]。

Human sRAGE is immobilized (10 μg/mL) overnight at 4°C in 96-well microtiter plates and blocked with 3% bovine serum albumin. 125I-labeled Aβ40, HMGB1, or S100B at 5 nM in the absence and presence of various concentrations of FPS2 or FPS-ZM1 (10 to 1,000 nM) is added to the wells containing immobilized sRAGE and incubated for 1 hour at room temperature in PBS. Wells are washed with cold PBS to remove unbound radiolabeled ligands, and the radioactivity is analyzed[1].

CHO cells are treated for 72 hours with different concentrations of inhibitors ranging from 10 nM to 10 μM. The cellular toxicity was determined using the WST-8 Assay Kit. (Only for Reference)