Dedicated DMPK for Degraders – a flexible approach for flexible molecules

Bifunctional degraders are compounds that bind to and induce degradation of a target by simultaneously binding to a ubiquitin ligase.¹ Despite their size and physical properties lying outside the space usually required for oral absorption (beyond the rule of 5, bRo5) there are many reports of bifunctional degraders with high levels of bioavailability and acceptable oral exposure levels in pre-clinical models.

However, challenges still exist due to the physicochemical space these molecules occupy and how well in vitro DMPK assays translate into in vivo performance. In this poster, we describe the assays and dedicated expertise at Sygnature Discovery aimed at supporting drug discovery projects involving bifunctional degraders, together with exemplar data for various compounds.