Discovery of a paralog-selective p300 protein degrader with potent anti-cancer activity in hematological malignancies
A new protein-degrading drug targets AML and lymphoma while avoiding toxicity that plagued earlier dual-target approaches, suggesting safer hematologic cancer options.
AbbVie researchers describe the first paralog-selective p300 protein degrader that avoids toxicity-causing CBP co-degradation seen with dual p300/CBP agents, demonstrating robust anti-tumor activity in AML, lymphoma, and myeloma xenograft models. The discovery of regioselective ubiquitination as a mechanism of paralog selectivity is mechanistically novel and may guide next-generation PROTAC design for hematologic malignancies.
What the study was
- Study design
- Preclinical (in vitro + xenograft)
- Category
- Drug Development
- Maturity
- Exploratory
- Journal
- Nature Communications
Why it surfaced
Novel PROTAC mechanism in AML/lymphoma/MM; triage_score capped at 5 per non-human study rule; industry source (AbbVie) indicates pipeline asset with likely near-term IND filing
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