Gamma-secretase is one of two protein-cutting enzymes responsible for the production of the amyloid protein of Alzheimer's disease, clipping amyoild out of its larger precursor protein APP. Although this enzyme is a top target for developing Alzheimer therapeutics, it also plays a critical role in normal human health by cutting another protein called the Notch receptor. Agents that block gamma-secretase lower amyloid levels but also cause toxic side effects by preventing proper cutting and functioning of the Notch receptor. Therefore, the identification of new agents that affect gamma-secretase to alter amyloid without interfering with Notch is essential. We have discovered three types of drug-like compounds that display these characteristics and now aim to optimize the structures of these compounds and test their ability to lower amyloid in Alzheimer mouse models.