L-685,458

L-685,458 inhibits Aβ(40) formation in both Neuro2A and CHO cell lines overexpressing human AβPP695, and in SHSY5Y cells overexpressing the construct spβA4CTF with IC50 of 402 nM, 113 nM, and 48 nM, respectively, with the potency for reduction of Aβ(42) being about 2-fold lower. ^[1] In Tca8113 cells, L-685,458 inhibits cell growth by inducing G0–G1 cell cycle arrest and apoptosis. ^[2] In a T-cell acute lymphoblastic leukemia cell line, pre-treatment with L-685,458 enhances the anti-proliferative effect of imatinib. ^[3] L685,458 also significantly reduces HSV-1 replication in tissue culture by inhibiting signal peptide peptidase (SPP). ^[4]

The in vitro growth rate of Tca8113 cells treated with L-685,458, is measured by MTT. Briefly, Tca8113 cells are seeded in 96-well plates. On the day of harvest, 100 μL of spent medium is replaced with an equal volume of fresh medium containing 10% MTT 5 mg ml−1 stock. Plates are incubated at 37°C for 4 h, then 100 μl of DMSO is added to each well, and then plates are shaken at room temperature for 10 min. The absorbance is measured at 570 nm.