2. Signaling Pathways
  3. Neuronal Signaling
  4. Beta-secretase
  5. BACE2 Isoform

BACE2

BACE2 (β-site APP-cleaving enzyme 2) is a type I transmembrane aspartyl protease that belongs to the β-secretase family and shares substantial sequence homology with BACE1, yet displays distinct substrate selectivity and physiological functions.[1][2] Mechanistically, BACE2 predominantly cleaves amyloid precursor protein (APP) within the Aβ region through θ-secretase-like activity, thereby reducing amyloidogenic processing and limiting Aβ generation in multiple experimental systems.[1][3][4] Beyond APP metabolism, BACE2 regulates ectodomain shedding of physiologically relevant substrates, including VEGFR3, and modulates lymphangiogenic VEGFR3 signaling by controlling receptor abundance and soluble VEGFR3 release.[2] In disease-associated contexts, BACE2 has been linked to Alzheimer’s disease, Down syndrome-related amyloid pathology, and age-dependent alterations in APP processing, where substrate conformation and cellular environment influence its proteolytic activity.[3][4][5] Compared with the closely related isoform BACE1, which functions as the principal β-secretase responsible for amyloidogenic APP cleavage, BACE2 generally exhibits anti-amyloidogenic activity and possesses distinct tissue distribution and substrate preferences.[1][2][4] Experimental studies further demonstrate that BACE2-mediated cleavage of TMEM27, PMEL, VEGFR3, and additional membrane proteins contributes to the regulation of glucose homeostasis, pigmentation, lymphatic signaling, and protein shedding pathways.[1][2] For research applications, selective discrimination between BACE1 and BACE2 activity remains essential during inhibitor development, as dual inhibition may alter physiological BACE2-dependent signaling and confound interpretation of therapeutic responses.[1][2]

BACE2 Related Products (6):

Cat. No. Product Name Effect Purity
  • HY-16759
    Verubecestat
    		Inhibitor 99.56%
    Verubecestat (MK-8931) is an orally active, high-affinity BACE1 and BACE2 inhibitor with Ki values of 2.2 nM and 0.38 nM. Verubecestat effectively reduces Aβ40 and has the potential for Alzheimer's Disease.
  • HY-136742
    BACE2-IN-1
    		Inhibitor 99.4%
    BACE2-IN-1 (compound 3l) is a highly selective BACE2 inhibitor with a Ki value of 1.6 nM. BACE2 inhibitors can be used to research of Type 2 Diabetes.
  • HY-124322
    NB-360
    		Inhibitor 99.08%
    NB-360 is a potent, brain penetrable and orally active β‐secretase 1/2 (BACE1/BACE2) dual inhibitor with IC50 values of 5 and 6 nM. NB-360 can inhibit amyloid-β protein accumulation. NB-360 can be used for the researches of inflammation and neurological disease, such as Alzheimer's disease.
  • HY-12938
    AMG-8718
    		Inhibitor
    AMG-8718 is a potent, selective and orally active BACE1 inhibitor with IC50 values of 0.0007, 0.005 µM for BACE1 and BACE2, respectively. AMG-8718 significantly decreases Aβ40 levels in the CSF and brain.
  • HY-147758
    BACE1/2-IN-1
    		Inhibitor
    BACE1/2-IN-1 (compound 34) is a potent BACE1 and BACE2 inhibitor, with an IC50 of 0.01 and 0.0053 μM, respectively. BACE1/2-IN-1 shows a combination of lower Pgp efflux ratio and improved passive permeability. BACE1/2-IN-1 displays reduced liver microsomal metabolic stability.
  • HY-161359
    BACE1-IN-14
    		Inhibitor
    BACE1-IN-14 (compound 27f) is a BACE1 inhibitor, with the EC50 values of 0.7 μM and 1.6 μM for BACE1 and BACE2. BACE1-IN-14 is can be used in Alzheimer's disease (AD) research.