SEN177 is a Glutaminyl cyclase (QPCT) inhibitor. Glutaminyl cyclase modifies N-terminal glutamine or glutamate residues to N-terminal 5-oxoproline or pyroglutamate (named QPCT). QPCT inhibits mutant huntingtin from forming aggregates, but also reduces aggregation of other aggregate-prone proteins containing polyQ or polyA repeats. SEN177 caused dose-dependent decreases in HTT aggregation by a mechanism that requires QPCT inhibition. SEN177 had in vitro activity against polyglutamine toxicity and was able to reduce aggregates in mammalian cells, primary neurons and in a Drosophila model.