AZD3839

AZD3839是BACE1的一种新型抑制剂，IC50值4.8μm [1]。

已报道用生化FRET分析表明AZD3839可抑制人BACE1活性。此外，AZD3839也被报道可抑制人SH-SY5Y细胞、鼠N2A细胞、小鼠和豚鼠的初级皮质神经元细胞释放sAPPβs。另外还表明AZD3839可有效地减少几内亚猪、老鼠和非人类的灵长类动物中脑脊液(CSF)、等离子体和大脑Aβ水平。AZD3839还可以减少C57BL/6小鼠初级皮层神经元（IC50 = 50.9 nmol/l）、N2A细胞(小鼠神经母细胞瘤)（IC50 = 32.2 nmol/l）和Dunkin-Hartley豚鼠初级皮层神经元（IC50 = 24.8 nmol/l）分泌Aβ40的水平[2]。

参考文献：
[1] Sparve E1, Quartino AL1, Luttgen M1, Tunblad K1, Teiling-Gardlund A1, Falting J1, Alexander R1, Kagstrom J1, Sjodin L1, Bulgak A1, Al-Saffar A1, Bridgland-Taylor M2, Pollard C3, Swedberg MD4, Vik T5, Paulsson B1. Prediction and modeling of effects on the QTc interval for clinical safety margin assessment, based on Single Ascending Dose study data with AZD3839. J Pharmacol Exp Ther. 2014 Jun 10.
[2] Jeppsson F1, Eketjll S, Janson J, Karlstrm S, Gustavsson S, Olsson LL, Radester AC, Ploeger B, Cebers G, Kolmodin K, Swahn BM, von Berg S, Bueters T, Flting J. Discovery of AZD3839, a potent and selective BACE1 inhibitor clinical candidate for the treatment of Alzheimer disease. J Biol Chem. 2012 Nov 30;287(49):41245-57.