FPS-ZM1

FPS-ZM1 is a high-affinity RAGE-specific blocker that inhibits amyloid-β binding to RAGE, neurological damage and inflammation in the APP(sw/0) transgenic mouse model of AD. FPS-ZM1 is not toxic to mice and can easily cross the blood-brain barrier. AGEs administration induced an-regulation of Abeta production, inflammation, and oxidative stress, and an increased escape latency of rats in the Morris water maze test, all of these are significantly reduced by FPS-ZM1 treatment. FPS-ZM1 might be a novel therapeutic agent to treat AD patients.

Product information

CAS Number: 945714-67-0

Molecular Weight: 327.85

Formula: C20H22ClNO

Synonym:

FPS ZM-1

Chemical Name: N-benzyl-4-chloro-N-cyclohexylbenzamide

Smiles: O=C(C1C=CC(Cl)=CC=1)N(CC1C=CC=CC=1)C1CCCCC1

InChiKey: XDFKWGIBQMHSOH-UHFFFAOYSA-N

InChi: InChI=1S/C20H22ClNO/c21-18-13-11-17(12-14-18)20(23)22(19-9-5-2-6-10-19)15-16-7-3-1-4-8-16/h1,3-4,7-8,11-14,19H,2,5-6,9-10,15H2

Technical Data

Appearance: Solid Power.

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: Soluble in DMSO, not in water

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥360 days if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

In Vitro:

FPS-ZM1 inhibits Aβ/RAGE binding in CHO cells with approximately 2-fold greater affinity than its parent molecule, FPS2. FPS-ZM1 inhibits binding of other known RAGE ligands to sRAGE, including S100 calcium-binding protein B and amphoterin. FPS-ZM1 is more effective than FPS2 in reducing Aβ40-induced increases inBACE1 mRNA and protein levels and the generation of sAPPβ, an APP cleavage product of BACE1 indicative of BACE1 activity.

In Vivo:

FPS-ZM1 is nontoxic to mice and readily crossed the blood-brain barrier. In aged APPsw/0 mice overexpressing human Aβ-precursor protein, a transgenic mouse model of AD with established Aβ pathology, FPS-ZM1 inhibits RAGE-mediated influx of circulating Aβ40 and Aβ42 into the brain. In brain, FPS-ZM1 binds exclusively to RAGE, which inhibits β-secretase activity and Aβ production and suppresses microglia activation and the neuro-inflammatory response. FPS-ZM1 treatment reduces the level of Aβ1-40 and Aβ1-42 in AGEs Rats. It Inhibits AGEs-mediated increase of Aβ-metabolism-related proteins and downregulates AGEs-mediated increase of pro-inflammatory cytokines in the hippocampus. FPS-ZM1 up-Regulates anti-oxidant defense system and attenuated AGEs induced memory impairment in AGEs rats.

References:

1. Hong Y, Shen C, Yin Q, Sun M, Ma Y, Liu X. Effects of RAGE-Specific Inhibitor FPS-ZM1 on Amyloid-β Metabolism and AGEs-Induced Inflammation and Oxidative Stress in Rat Hippocampus. Neurochem Res. 2016 May;41(5):1192-9. doi: 10.1007/s11064-015-1814-8. Epub 2016 Jan 6. PubMed PMID: 26738988.
2. Chen Y, Huang XJ, Yu N, Xie Y, Zhang K, Wen F, Liu H, Di Q. HMGB1 Contributes to the Expression of P-Glycoprotein in Mouse Epileptic Brain through Toll-Like Receptor 4 and Receptor for Advanced Glycation End Products. PLoS One. 2015 Oct 20;10(10):e0140918. doi: 10.1371/journal.pone.0140918. eCollection 2015. PubMed PMID: 26485677; PubMed Central PMCID: PMC4613137.
3. Li D, Lei C, Zhang S, Zhang S, Liu M, Wu B. Blockade of high mobility group box-1 signaling via the receptor for advanced glycation end-products ameliorates inflammatory damage after acute intracerebral hemorrhage. Neurosci Lett. 2015 Nov 16;609:109-19. doi: 10.1016/j.neulet.2015.10.035. Epub 2015 Oct 23. PubMed PMID: 26483322.

Products are for research use only. Not for human use.