Targeted degradation of CBP/p300 by CBPD-409 exhibits robust anti-myeloma activity
Epigenetic regulation is central to multiple myeloma (MM) pathogenesis. Among the most critical regulators are the histone acetyltransferases CREB‑binding protein (CBP) and p300, which act as transcriptional co‑activators that maintain MYC‑driven proliferation, IRF4‑dependent survival, and plasma cell identity [ 1 ]. Pharmacologic inhibition of CBP/p300 bromodomains with CCS1477/inobrodib has shown early clinical activity in a phase 2 trials (NCT04068597) for MM, confirming these co‑activators as actionable targets [ 2 ]. However, inhibitors act via occupancy‑driven pharmacology, suppressing only catalytic function while leaving intact the non‑enzymatic scaffolding roles that are critical for oncogenic transcription [ 3 ]. As a result, their efficacy is incomplete.
Authors
- S. Corradini (ORCID: https://orcid.org/0000-0002-5990-806X)
- Mark Williams (ORCID: https://orcid.org/0000-0003-1114-1418)
- Mina Maksimos (ORCID: https://orcid.org/0009-0006-9354-6556)
- R. Soutar
- Abdel Kareem Azab (ORCID: https://orcid.org/0000-0002-6371-2780)
- Shaomeng Wang (ORCID: https://orcid.org/0000-0002-8782-6950)
- F. Azab
- Z. Chen
- J. Travers
- S. Arsalani
- R. Henderson
- E. Nwarunma (ORCID: https://orcid.org/0009-0009-2543-2508)
- M. Powell
- G. Watt
Institutions
- Fujian Medical University (CN)
- Glasgow Caledonian University (GB)
- University of Michigan (US)
- Beatson West of Scotland Cancer Centre (GB)
- Southwestern Medical Center (US)
- Michigan Medicine (US)
- Fujian Provincial Hospital (CN)
- University of Glasgow (GB)
- The University of Texas Southwestern Medical Center (US)
Publication Details
- Journal
- Leukemia
- Published
- 2026-06-16
- DOI
- https://doi.org/10.1038/s41375-026-03004-2
- Primary Topic
- Protein Degradation and Inhibitors
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Cancer Prevention and Research Institute of Texas
- Glasgow Caledonian University
- Academy of Finland