The cis/trans isomerization of X-Pro peptide bonds in proteins in some instances acts as a molecular switch in biological pathways. Our prior work suggests that the cis isomer of the phospho-Thr668-Pro669 motif， located in the cytoplasmic domain of the amyloid-β protein precursor (AβPP)， is correlated with an increase in amyloidogenic processing of AβPP and production of amyloid-beta (Aβ)， the neurotoxic peptide fragment in Alzheimer's disease (AD). We designed a 100% cis-locked cyclic dipeptide composed of cyclized phospho-Thr-Pro (pCDP) as a mimic for this putative pathological conformation， and three phosphate-blocked derivatives (pCDP-diBzl， pCDP-Bzl， and pCDP-diPOM). Two H4 neuroglioma cell lines were established as AD cell models for use in testing these compounds: H4-AβPP695 for stable overexpression of wild-type AβPP695， and H4-BACE1 for stable overexpression of β-site AβPP cleaving enzyme-1 (BACE1). The level of the secreted AβPP fragment resulting from BACE1 activity， sAβPPβ， served as a key proxy for amyloidogenic processing， since cleavage of AβPP by BACE1 is a requisite first step in Aβ production. Of the compounds tested， pCDP-diBzl decreased sAβPPβ levels in both cell lines， while pCDP-diPOM decreased sAβPPβ levels in only H4-BACE1 cells， all with similar dose-dependences and patterns of proteolytic AβPP fragments. Enzymatic assays showed that none of the pCDP derivatives directly inhibit BACE1 catalytic activity. These results suggest a model in which pCDP-diBzl and pCDP-diPOM act at a common point to inhibit entry of AβPP into the amyloidogenic AβPP processing pathway but through different targets， and provide important insights for the development of novel AD therapeutics.