DW-229
DW-229 is a PROTAC degrader derived from Deferiprone (HY-B0568), targeting Fe(II)/α‑ketoglutarate‑dependent histone lysine demethylases (KDMs). DW-229 degrades KDM2A, KDM3A, KDM5B, KDM4A‑C, KDM5C, KDM6B in breast cancer cells. DW-229 shows IC50 < 0.5 μM against MCF‑7 cells and IC50 of 8.87 μM against MDA‑MB‑231 cells, with high cancer cell selectivity. DW-229 can be used for the research of breast cancer, liver cancer, prostate cancer, lung cancer.
(Pink: Histone Demethylase ligand (HY-B0568); Blue: Cereblon ligand (HY-41547); Black: linker).
For research use only. We do not sell to patients.
- Formula: C38H41N5O7
- Molecular Weight:679.76
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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
- Protocols
- Purity & Documentation
- References
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Help & FAQs
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Biological Activity
Description
IC50 & Target
[1]|
Cereblon |
KDM2 |
KDM3 |
KDM4A |
KDM5B |
KDM6 |
In Vitro
DW-229 binds to purified E3 ligase and Fe2+/α-ketoglutarate-dependent KDMs (KDM6A, KDM5A, KDM5B, KDM3A, KDM2A)[1].
DW-229 (0.1-2.5 μM; 48 h) inhibits KDM activity in mES cells in a dose-dependent manner, with a transient heterochromatin-inducing effect at lower concentrations[1].
DW-229 (72 h) potently inhibits the proliferation of multiple cancer cell lines (A549, DU-145, LNCaP, HepG2, SK-HEP-1, MCF-7, MDA-MB-231, MDA-MB-453) with IC50 values ranging from < 0.5 μM to 8.87 μM, while showing minimal cytotoxicity against normal Vero cells[1].
DW-229 (0.5-8.0 μM; 24 h) significantly downregulates nuclear KDM5B and KDM6A expression in MCF-7 breast cancer cells[1].
DW-229 (2.5-40 μM; 24 h) exerts a biphasic effect on cytoplasmic KDM1A expression in MDA-MB-231 breast cancer cells[1].
DW-229 (0.9 μM; 24 h) downregulates the expression of multiple KDM genes in MCF-7 breast cancer cells, strongly reducing KDM2A, KDM3A, and KDM5B levels, and moderately reducing KDM4A-C, KDM5C, and KDM6B levels[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:MCF-7 breast cancer cells
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Concentration:0.5, 1.0, 2.0, 4.0, 8.0 μM
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Incubation Time:24 h
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Result:Significantly downregulated nuclear expression levels of KDM5B and KDM6A.
Had minimal effects on cytoplasmic and nuclear KDM1A, and cytoplasmic KDM6B.
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Cell Line:MDA-MB-231 breast cancer cells
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Concentration:2.5, 5, 10, 20, 40 μM
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Incubation Time:24 h
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Result:Exerted a biphasic effect on cytoplasmic KDM1A expression, with downregulation at lower concentrations and upregulation at higher concentrations.
Affected nuclear KDM1A expression only via upregulation at the highest concentration.
Exerted a nonsignificant biphasic effect on cytoplasmic KDM6B expression.
Showed no significant effect on nuclear KDM5B.
Chemical Information
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Molecular Weight 679.76
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Formula C38H41N5O7
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SMILES
O=C1N(C2C(NC(CC2)=O)=O)C(C3=CC=CC(NCCCCC#CC4=CC(C(NCCCCCCN5C(C)=C(O)C(C=C5)=O)=O)=CC=C4)=C31)=O
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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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Cell Cytotoxicity Assay
Cytotoxicity assays are usually based on the assessment of cell membrane damage, which can also be indirectly detected by measuring cell viability. Detection methods include MTT assay, CKK-8 assay, LDH assay and ATP assay, etc.
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Liver Cancer Modeling
Liver cancer can be classified into primary liver cancer and secondary liver cancer. Secondary liver cancer is the metastatic liver cancer. Primary liver cancer includes hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC) and fibrolamellar HCC, of which HCC is the most common form, accounting for approximately 90% of primary liver cancers[1]. HCC mouse models include chemical agent-induced models, transplanted tumor models, and genetic engineered models.
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Breast Cancer Modeling
Breast cancer is a heterogeneous cancer, and it has been distinguished into four subtypes: luminal A, luminal B, HER2-positive and basal-like. Molecular mutations, epigenetic alterations, hormone exposure and immune microenvironment are related to the progression of breast cancer.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
DW-229 Related Classifications
HY-183618 Related Classifications
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