Abstract
Icenticaftor (QBW251) is a potentiator of the CFTR protein which was under development for treatment of COPD and chronic bronchitis by Novartis. In humans it is extensively metabolised. Direct N-glucuronidation and O-glucuronidation formed the most abundant human metabolites M8 and M9, respectively. [1].
Initial amounts of M8 and M9 were made for MetID purposes using biotransformation with rabbit liver S9 fraction [1]. For further testing and analysis method calibration in later phase studies, more material was required of M8 and M9, and also of M5, which is formed following demethylation of icenticaftor and subsequent O-glucuronidation. Alternative scalable methods were subsequently used to generate this material using a combination of late-stage chemical synthesis (M5) and microbial biotransformation (M8 and M9). This poster describes the application of microbial biotransformation [2,3] to make scalable amounts of M8 and M9.
Poster presented at ISSX2025 by Julia Shanu-Wilson