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BMS-986418
- Development stage
- Unknown
- Lead developer
- Bristol Myers Squibb
- Modality
- Molecular Glues → Targeted Protein Degraders (TPDs) → Small Molecules
- Administration
- Oral
01
Overview
BMS-986418 is an investigational, orally bioavailable small molecule CELMoD (Cereblon E3 Ligase Modulator) developed by Bristol Myers Squibb for the treatment of sickle cell disease. It functions as a molecular glue that facilitates the recruitment of the cereblon E3 ubiquitin ligase complex to the transcriptional repressors ZBTB7A (also known as LRF) and Wiz. This interaction leads to the ubiquitination and subsequent proteasomal degradation of these repressors, which are known to inhibit the expression of fetal hemoglobin (HbF). By reactivating HbF production in erythroid cells, BMS-986418 aims to achieve therapeutic levels of HbF (at least 30% total HbF) to inhibit the polymerization of sickle hemoglobin (HbS), thereby preventing red blood cell sickling and ameliorating the clinical symptoms of sickle cell disease. It is currently in Phase 1 clinical development.
- Other names
- fetal hemoglobin activating cereblon E3 ligase modulatorHbF-activating CELMoDZBTB7A/Wiz degrader
02
Targets
ZBTB7A (Zinc finger and BTB domain-containing protein 7A)CRBN (Cereblon)WIZ (WIZ zinc finger protein)
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