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bms-986458
- Development stage
- Phase 2
- Lead developer
- Bristol Myers Squibb
- Modality
- PROTACs (E3 ligase recruitment) → Targeted Protein Degraders (TPDs) → Small Molecules, Bivalent/Multivalent Binders → Multivalent & Scaffold-Based Small Molecules → Small Molecules
- Administration
- Oral
01
Overview
BMS-986458 is an investigational, oral, small molecule ligand-directed degrader (LDD) that targets the B cell lymphoma 6 protein (BCL6). It functions as a bifunctional cereblon-dependent agent that binds to both BCL6 and E3 ubiquitin ligase, leading to targeted degradation of the BCL6 protein in tumor cells. This mechanism results in broad anti-tumor effects by modulating cell-cycle checkpoints, anti-proliferative signaling, and interferon response pathways. Notably, it enhances CD20 expression on lymphoma cells and shows synergistic activity with anti-CD20 agents. Developed by Bristol Myers Squibb for the treatment of relapsed/refractory non-Hodgkin lymphomas—including diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma—BMS-986458 is currently being evaluated in Phase I/II clinical trials[1][2][3][4][5][7].
- Other names
- BCL6 degrader BMS-986458BCL-6 degrader BMS-986458BCL 6 degrader BMS-986458
02
Targets
CRBN (Cereblon)BCL6 (B cell lymphoma 6 protein)
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