Application of Plexium’s Picowell Screening Technology to the Identification of IKZF2 Molecular Glue Degraders
The present disclosure describes the successful application of Plexium’s Picowell screening technology to the identification of IKZF2 (Helios) molecular glue degraders (MGDs). This approach involved generation of a large One-Bead-One-Compound cereblon targeted chemical library, in which the beads are encoded with DNA tags, and the compounds are orthogonally attached to the beads through a photocleavable linker. Upon irradiation and release, compounds unencumbered with DNA tags are screened utilizing an ultrahigh density ‘picowell’ screening platform in phenotypic
cellular assays that enabled identification of potential MGDs that promote depletion of IKZF2. The technology enables the rapid generation and screening of 100,000’s of compounds, with dense coverage of chemical space, in a cost-effective and efficient manner and is applicable to numerous proteins of interest (POIs) and a variety assay types