PROTAC IKZF3 degrader-1
PROTAC IKZF3 degrader-1 is a potent dual-targeting agent that functions as both a CARM1 inhibitor (IC50 = 2 nM) and a CRBN-dependent PROTAC degrader of IKZF3. PROTAC IKZF3 degrader-1 simultaneously inhibits CARM1 activity (reducing BAF155 methylation) and recruits CRBN to induce the targeted degradation of IKZF1, IKZF3, ZFP91, and FGD3 proteins; this leads to the downregulation of oncogenes, more potent induction of apoptosis, and the overcoming of immunomodulatory imide drugs resistance. PROTAC IKZF3 degrader-1 is suitable for research into both IMiD-sensitive and IMiD-resistant multiple myeloma.
(Pink: IKZF3 ligand (HY-172369); Blue: Cereblon ligand (HY-41547); Black: linker (HY-21999)).
For research use only. We do not sell to patients.
- Formula: C46H54ClN9O8
- Molecular Weight:896.43
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
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IKZF3 |
PROTAC IKZF3 degrader-1 (Compound 074) (0.1-1000 nM; 6 days) significantly and selectively inhibits the proliferation of myeloma cells (H929, MM.1S, and U266) while exhibiting minimal cytotoxicity toward normal bone marrow (BM) cells[1].
PROTAC IKZF3 degrader-1 (312.5-1250 nM; 24-48 h) downregulates methylated BAF155 levels and induces the degradation of IKZF1, IKZF3, and MYC proteins in H929 cells[1].
PROTAC IKZF3 degrader-1 (1250 nM; 6-48 h) significantly downregulates IKZF3 protein expression in H929 and 8226 cells without causing significant degradation of the CARM1 protein[1].
PROTAC IKZF3 degrader-1 (10-1000 nM; 24 h) downregulates MYC protein expression in 8226 cells[1].
PROTAC IKZF3 degrader-1 (2.5 μM; 8-24 h) specifically degrades IKZF1, IKZF3, ZFP91, and FGD3 proteins in MOLT-4 cells[1].
PROTAC IKZF3 degrader-1 (1-1000 nM; 24 h) degrades ZFP91, IKZF1, IKZF3, and FGD3, and potently downregulates MYC protein in H929 cells[1].
PROTAC IKZF3 degrader-1 (1-1000 nM; 5 days) inhibits cell proliferation in a CRBN-dependent manner in MM.1S and MM.1S CRBN KO cells, and exhibits stronger antiproliferative activity in H929 cells compared to a control compound (MTG-3-141) lacking CRBN-binding capability[1].
PROTAC IKZF3 degrader-1 (10-1000 nM; 24 h) induces CRBN-dependent target protein degradation in MM.1S and MM.1S CRBN KO cells[1].
PROTAC IKZF3 degrader-1 (25-400 nM; 6 days) overcomes IMiD resistance and effectively inhibits cell growth in pomalidomide (HY-10984)-resistant H929 cells[1].
PROTAC IKZF3 degrader-1 (0.1-1000 nM; 1-4 days) induces late-stage apoptosis and necrosis in H929 cells in a concentration-dependent manner and downregulates MYC and IRF4 mRNA transcription levels[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:H929, MM.1S, U266, and normal BM cells
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Concentration:0.1, 1, 10, 100, 1000 nM
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Incubation Time:6 days
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Result:Significantly inhibited myeloma cell proliferation while exhibiting minimal toxicity to normal bone marrow cells.
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Cell Line:H929 cells
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Concentration:312.5, 625, 1250 nM
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Incubation Time:24, 48 h
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Result:Reduced methylated BAF155 levels and downregulated IKZF1, IKZF3, and MYC protein expression.
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Cell Line:H929 and 8226 cells
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Concentration:1250 nM
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Incubation Time:6, 24, 48 h
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Result:Significantly downregulated IKZF3 protein expression without noticeably degrading CARM1 protein.
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Cell Line:8226 cells
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Concentration:0.1, 1, 10, 100, 1000 nM
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Incubation Time:24 h
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Result:Downregulated MYC protein expression.
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Cell Line:H929 cells
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Concentration:1, 10, 100, 1000 nM
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Incubation Time:24 h
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Result:Degraded ZFP91, IKZF1, IKZF3, and FGD3 and downregulated MYC protein more potently than pomalidomide.
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Cell Line:MM.1S and MM.1S CRBN KO cells
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Concentration:1, 10, 100, 1000 nM
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Incubation Time:5 days
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Result:Exerted potent growth inhibition in wild-type cells, whereas this activity was significantly attenuated in CRBN-knockout cells, indicating that its anti-proliferative effect is CRBN-dependent.
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Cell Line:MM.1S and MM.1S CRBN KO cells
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Concentration:10, 100, 1000 nM
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Incubation Time:24 h
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Result:Degraded FGD3, ZFP91, IKZF1, and IKZF3 in wild-type cells, but no significant degradation was observed in CRBN-knockout cells, indicating that the targeted degradation is CRBN-dependent.
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Cell Line:H929 cells
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Concentration:1, 10, 100, 1000 nM
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Incubation Time:5 days
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Result:Exhibited stronger proliferation inhibition compared to the control lacking CRBN-binding activity (MTG-3-141).
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Cell Line:Pomalidomide-resistant H929 cells
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Concentration:25, 50, 100, 200, 400 nM
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Incubation Time:6 days
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Result:Effectively inhibited the growth of resistant cells, overcoming IMiD resistance.
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Cell Line:H929 cells
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Concentration:0.1, 1, 10, 100, 1000 nM
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Incubation Time:4 days
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Result:Induced late-stage apoptosis and necrosis in a concentration-dependent manner.
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Cell Line:H929 cells
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Concentration:0.1, 1, 10, 100, 1000 nM
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Incubation Time:24 h
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Result:Significantly downregulated the mRNA transcription levels of MYC and IRF4.
Chemical Information
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Molecular Weight 896.43
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Formula C46H54ClN9O8
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SMILES
ClC1=C(C2=NC(C3=C(C)ON=C3C)=C(C)C(N4CC5(CCN(C(CCCCCNC6=C(C(N(C7C(NC(CC7)=O)=O)C8=O)=O)C8=CC=C6)=O)CC5)C4)=N2)C=C(OC[C@@H](CNC)O)C=C1
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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.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
PROTAC IKZF3 degrader-1 Related Classifications
HY-172368 Related Classifications
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