FPS-ZM1 is a receptor for Advanced Glycation End products (RAGE) inhibitor (IC50 = 0.6 μM). It decreases the amount of Aβ by binding to the V domain of RAGE. It also blocks multiple mechanisms of Aβ40- and Aβ42-induced cellular stress in RAGE-expressing brain endothelium, neurons, and microglia in vitro and in vivo (1,2). FPS-ZM1 has also shown the ability to cross the BBB. In a rat model, it was able to cross the blood-brain barrier and cause white matter fiber damage (3). FPS-ZM1 inhibition of RAGE was able to ameliorate inflammatory damage after acute intracerebral hemorrhage via downstream blockade of high mobility box-1(HMGB1) signaling (4). Lastly, it also plays a role in breast cancer cell invasion and metastasis, impairing it (5).
1) Deans et al. (2012), A multimodal RAGE-specific inhibitor reduces amyloid β-mediated brain disorder in a mouse model of Alzheimer disease; J.Clin.Invest. 122 1377
2) Hong et al. (2016), Effects of RAGE-Specific Inhibitor FPS-ZM1 on Amyloid-β Metabolism and AGEs-Induced Inflammation and Oxidative Stress in Rat Hippocampus; Neurochem.Res. 41 1192
3) Yang et al. (2015), Receptor for advanced glycation end-product antagonist reduces blood-brain barrier damage after intracerebral hemorrhage; Stroke 46 1328
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