BMS-986449
BMS-986449 is a potent and orally active CELMoD molecular glue and an IKZF2/IKZF4 degrader. BMS-986449 targets the degradation of transcription factors Helios (IKZF2) and Eos (IKZF4) in regulatory T (Treg) cells. BMS-986449 redirects the E3 ubiquitin ligase Cereblon to induce the degradation of Helios and Eos, reprogramming Treg cells and enhancing antitumor immunity. BMS-986449 is promising for research of advanced solid tumors.
For research use only. We do not sell to patients.
- Formula: C21H21FN4O3
- Molecular Weight:396.41
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
Biological Activity
Description
IC50 & Target
[1]|
IKZF2 |
IKZF4 |
In Vitro
Upon activation culture, human primary Treg cells treated with BMS‑986449 has a reprogrammed transcriptional phenotype by day 8: increased protein expression of effector molecules (e.g., Granzyme B) and abundant expression of inflammatory gene transcripts[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
In Vivo
BMS‑986449 has antitumor activity in the CT26, MB49, and MC38 tumor models in human CRBN knock‑in tumor‑bearing mice, with maximum tumor growth inhibition (TGI) values of up to 75%, 62%, and 42%, respectively. When combined with anti‑PD‑1 immune checkpoint inhibitor, the efficacy was significantly enhanced, with TGI values of 95%, 97%, and 92%, respectively[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Clinical Trial
| NCT Number | Sponsor | Condition | Start Date |
Phase
|
|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
Chemical Information
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Molecular Weight 396.41
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Formula C21H21FN4O3
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SMILES
NC1=NC(C2=C(F)C([C@@H](C)N([C@H]3CCC(NC3=O)=O)C4=O)=C4C=C2)=CC(C)=C1C
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Protocols
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Naïve CD4+ T-cell subset differentiation/polarization
Naïve CD4+ T-cell subset differentiation/polarization is an in vitro assay in which purified naïve CD4+ T cells are activated through TCR and CD28 costimulation and cultured with defined cytokines and neutralizing antibodies to generate Th0, Th1, Th2, Th17, or induced Treg-like populations. Differentiation is detected by subset-associated cytokines and transcription factors: IFN-γ/T-bet for Th1, IL-4/GATA3 for Th2, IL-17A/RORγt for Th17, and Foxp3 for induced Treg cells. The assay readout is usually generated by intracellular cytokine staining after restimulation, transcription-factor staining by flow cytometry, ELISA of secreted cytokines, or gene-expression analysis. The result reflects cytokine-directed lineage commitment or polarization rather than antigen-specific immune protection by itself.
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Research Protocol for Cancer Immunology
Cancer immunology studies how the immune system recognizes, suppresses, edits, or fails to eliminate malignant cells through tumor antigen release, antigen presentation, T-cell priming, immune trafficking, tumor-cell killing, and feedback inhibition in the tumor microenvironment. The cancer-immunity cycle links tumor antigenicity, dendritic-cell priming, CD8+ T-cell infiltration, cytotoxic function, and immune-checkpoint regulation to tumor rejection or immune escape. Immune-checkpoint pathways such as PD-1/PD-L1 and CTLA-4 suppress antitumor T-cell activity and can be therapeutically blocked, but many tumors remain resistant because of poor antigen presentation, weak T-cell infiltration, suppressive myeloid cells, regulatory T cells, and tumor-intrinsic immune-exclusion programs. Unresolved questions include which immune-cell states predict response, how tumor-intrinsic pathways exclude immune cells, how myeloid suppression limits checkpoint blockade, and which combination strategies
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)