IKZF2-degrader 2
IKZF2-degrader 2 is a selective and orally active IKZF2 molecular glue degrader with DC50 values of 0.5 nM and 1.8 nM in HiBit and FACS. The IKZF2-degrader 2 mediates the ubiquitination and degradation of target proteins by recruiting the CRL4-CRBN E3 ubiquitin ligase. IKZF2-degrader 2 displays moderate degradation against SALL4 with a DC50 of 9 nM but does not induce any significant degradation towards IKZF1, IKZF3, CK1α and GSPT1. IKZF2-degrader 2 can be used for the study of cancer immunology.
For research use only. We do not sell to patients.
- CAS No.: 2983841-00-3
- Formula: C26H25ClFN5O3
- Molecular Weight:509.96
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
Biological Activity
Description
IC50 & Target
[1]|
IZKF2 0.5 nM (DC50) |
In Vitro
IKZF2-degrader 2 (Compound 55) (41 nM-10 μM, 6 h) is a highly selective IKZF2 degrader with minimal off-target neo-substrate degradation in Jurkat cells[1].
IKZF2-degrader 2 (1 μM) exhibits excellent metabolic stability in human, crab-eating monkey, rat and mouse liver microsomes, especially in the human[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
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Cell Line:Jurkat cells and CRBN knockout (KO) Jurkat cells
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Concentration:41, 123, 370, 1111, 3333 and 10000 nM
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Incubation Time:6 h
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Result:Selectively degraded IKZF2 without impacting IKZF1, CK1α, or GSPT1.
Was completely lost in CRBN KO cells, confirming CRBN-mediated activity.
Parmacokinetics
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:PK/PD evaluation in immune competent established in gene-edited C57BL/6 mice harboring humanized CRBNMI391 V protein[1]
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Dosage:10 and 30 mg/kg
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Administration:Oral gavage (i.g.), single dose
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Result:Showed profound IKZF2 degradation at 6 h which was attenuated at 24 h in both spleen and thymus tissues.
Was comparable with that in thymus in spleen, while 8-fold higher drug exposures in spleen was observed than that in thymus.
Chemical Information
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CAS No. 2983841-00-3
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Molecular Weight 509.96
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Formula C26H25ClFN5O3
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SMILES
O=C1C2=C(CN1C3C(NC(CC3)=O)=O)C(F)=C(C4=C(Cl)C(CN5CCCC5)=C(C=CN6C)C6=N4)C=C2
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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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Fluorescence activated cell sorting
Fluorescence activated cell sorting (FACS) is a special technology for identifying and separating rare cell populations with high purity.
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Fluorescence-Activated Cell Sorting (FACS)-Based Cell Sorting
Fluorescence-Activated Cell Sorting (FACS) separates cells in suspension after flow-cytometric measurement of light scatter and fluorescence; classic droplet-based instruments interrogate cells with a laser, convert optical signals into electronic signals, charge droplets containing target cells, and electrostatically deflect them into collection vessels. FACS detects phenotypes defined by fluorescent antibodies, fluorescent proteins, viability dyes, or intracellular markers, and the readout is the sorted fraction, purity, recovery, and post-sort viability of the gated population.
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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)