Topic
Therapeutic strategies that redirect ubiquitin ligase machinery to degrade chosen proteins.
A Baylor College of Medicine team used a structure-prediction workflow called GluePlex to find where a molecular glue grips the protein VAV1 before any experiment showed it. A separate group later reached the same conclusion in the lab.
Reality
CeMM and Oxford researchers degraded the protein NUDT5 in cells and made them resistant to 6-thioguanine, while inhibiting the same enzyme had little effect. The split separates what the protein catalyses from what it does by being present.
Reality
Orum halted an earlier antibody-degrader conjugate in April last year after a death and unexplained liver toxicity. The candidate Bristol Myers is testing in leukemia sits on the same platform, and a second in-house candidate uses the same degrader.
Reality
Steven Banik's group treats sub-threshold protein changes as a detection problem rather than a biological one. Their engineered readout is meant to hold its signal in small numbers of cells, which is what a screen actually needs.
Reality
Peisheng Xu's group degraded the PTBP1 protein with antibodies ferried past the blood-brain barrier, and human astrocytes in a dish turned into firing neurons. In living mice, the lineage question is still open.
Perspective Coverage
3 publishersReality
A Nature Communications model from Weill Cornell argues that a target protein's turnover rate can matter as much as how tightly a degrader binds it, which would reorder where degrader programs spend their optimisation money.
Reality
A Warsaw group has indexed the substrate receptors of cullin-RING ligases and mapped their disease links, giving rare-disease geneticists a specific failure to test rather than a gene name.
Reality