[CAS NO. 1383982-64-6]  Lanabecestat (AZD3293)

Lanabecestat（AZD3293, LY3314814）is a potent, highly permeable, orally active, blood-brain barrier (BBB) penetrating, BACE1 inhibitor with unique slow off-rate kinetics. When the potency of AZD3293 with respect to secretion of Aβ40 and sAβPPβ is studied in a range of cellular models, the compound displays pM potency in primary neuron cultures from mice and guinea pigs and in SH-SY5Y cells over-expressing AβPP (IC50 = 610 pM, 310 pM, and 80 pM, respectively). AZD3293 is also tested in a panel of more than 350 in vitro radioligand binding and enzyme activity assays, covering a diverse range of receptors, ion channels, transporters, kinases, and enzymes, up to a concentration of 10μM of AZD3293. A few significant responses are observed, but these had at least a 1,000-fold selectivity against BACE1, thus indicating specificity to BACE1. The off-rate of AZD3293 has an estimated t of approximately 9 h.