AZ1136

AZ1136 (25 μM; 2 h) modulates γ-secretase-mediated APP processing in HEK/APPswe cell membranes, reduces the levels of Aβ42 and Aβ40, increases the levels of short-chain Aβ37 and Aβ38, alters specific short peptide cleavage products, and preferentially affects the turnover of Aβ42 without inhibiting the overall activity of γ-secretase^[1].
AZ1136 modulates γ-secretase-mediated Aβ production in HEK/APPswe cells, potently reduces the levels of amyloidogenic Aβ42 (IC₅₀ = 990 nM) and Aβ40 (IC₅₀ = 1400 nM), while increasing the shorter, less amyloidogenic Aβ37 and Aβ39, without altering total Aβ levels^[2].
AZ1136 (25 μM; 16 h) reduces Aβ40 and Aβ42 by 2.3-fold and 8.3-fold, respectively, increases Aβ37 and Aβ39 by 3.5-fold and 2.1-fold, respectively, in HEK/APPswe cells, while Aβ38 remains unaffected^[2].
AZ1136 (5 h) modulates γ-secretase-mediated APP processing in HEK/APPswe cells, reduces the levels of Aβ42 (IC₅₀ 990 nM) and Aβ40 (IC₅₀ 1400 nM) (with higher potency against Aβ42), and increases the shorter Aβ37 and Aβ39 peptides, without altering total Aβ levels or inducing cytotoxicity^[3].
AZ1136 (0-5 μM; 5 h) competes with AZ4800 for binding to a common molecular target in HEK/APPswe cells, indicating that both belong to the same class of second-generation γ-secretase modulators^[3].
AZ1136 (2 h) retains Aβ-modulating activity in both HEK/APPswe-derived total membranes (TM) and carbonate-extracted membranes (CEM), significantly inhibiting Aβ42 and increasing Aβ37; a slight increase in Aβ38 is also observed in this cell-free membrane assay^[3].

AZ1136 (25 μM; 24 h) modulates γ-secretase-mediated Notch N peptide production in HEK/FLAG-Notch1-ΔE cells, reducing F-N24 and F-N25 by 2.0-fold and 2.6-fold, respectively, and increasing F-N18 by 1.7-fold^[2].