Abstract: The identification of new acetylcholinesterase (AChE) inhibitors is described. For example, tilorone was newly identified as an AChE inhibitor by use of a machine learning model followed by in vitro screening. The new AChE inhibitors can selectively inhibit AChE compared to butyrylcholinesterase (BuChE). Methods of inhibiting AChE and of treating or preventing diseases, disorders, and conditions treatable or preventable by AChE inhibition are also described. For example, methods of treating and/or preventing certain dermatological conditions and organophosphorous or nerve agent poisoning are described.