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Targeted protein degradation (TPD) mediates protein level through small molecule induced redirection of E3 ligases to ubiquitinate neo-substrates and mark them for proteasomal degradation. TPD has recently emerged as a key modality in drug discovery. So
In addition, as a rationale to have potentially a higher bar for emerging resistance mechanisms on the ligase side, we analyzed this subset of 48 E3 receptors for essentiality by extracting the Demeter2 dependency scores from the DepMAP database23,32. Inter- estingly, the mainly nuclear ...