SEN177 is a potent glutaminyl cyclase (QPCT) inhibitor with an IC50 of 0.013μM for glutaminyl-peptide cyclotransferase-like (QPCTL). SEN177 has a Ki of 20 nM for human glutaminyl cyclase (hQC). SEN177 greatly reduces the early stages of mutant HTT oligomerisation and reduces the percentage of neurons with Q80 aggregates. SEN177 has the potential for Huntington's disease research[1].
[1]. Meike E W Logtenberg, et al. Glutaminyl cyclase is an enzymatic modifier of the CD47- SIRPα axis and a target for cancer immunotherapy. Nat Med
[2]. Cecilia Pozzi, et al. The structure of the human glutaminyl cyclase-SEN177 complex indicates routes for developing new potent inhibitors as possible agents for the treatment of neurological disorders. J Biol Inorg Chem. 2018 Dec;23(8):1219-1226.
[3]. Maria Jimenez-Sanchez, et al. siRNA screen identifies QPCT as a druggable target for Huntington's disease. Nat Chem Biol. 2015 May;11(5):347-354.