Discovery of penicillic acid as a chemical probe against tau aggregation in Alzheimer's disease
Jennifer Shyong, Jinliang Wang, Quoc-Dung Tran Huynh, Marina Fayzullina, Bo Yuan, Ching‐Kuo Lee, Thomas G. Minehan, Paul M. Seidler, Clay C. C. Wang · Chemical Science · 2024
experiments reveal that penicillic acid directly inhibits tau by disaggregating fibrils. Although penicillic acid possesses blood-brain barrier penetrability properties that are computationally predicted to be favorable, it is presumed to contain some mutagenic effects as well. To address this, we used the backbone of penicillic acid as a chemical probe to discover similar compounds that can inhibit AD tau aggregation with limited mutagenicity. This work suggests the potential of discovering chemical probes through natural product screening for small-molecule drug discovery of tauopathies.