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Cat. No.: HY-183717

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M4K3233

M4K3233 is a selective ALK2 PROTAC degrader with a pDC₅₀ of 7.3 and a pIC₅₀ of 6.6. M4K3233 recruits CRBN to form a ternary complex with ALK2, mediating ALK2 degradation via the proteasomal and lysosomal pathways. M4K3233 induces moderate downregulation of RIPK2 and significant downregulation of SIK3 in mammalian cells. M4K3233 is applicable to research related to glioblastoma.
(Pink: ALK2 ligand (HY-149591); Blue: Cereblon ligand (HY-14658); Black: linker).

연구목적의 판매만을 진행합니다. 환자를 대상으로 한 판매는 하지 않습니다.

화학식: C₄₄H₄₈N₆O₇
분자량:772.89

보관:

Please store the product under the recommended conditions in the Certificate of Analysis.

M4K3233 Chemical Structure

사이즈

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Use of MCE Products

Fluorescent Dye

Strong Fluorescence Signal / Multi-Disciplinary Applications / High Fluorescence Specificity

Biological Activity
- 제품 설명
- In Vitro
Chemical Information
순도&문서
References
Calculators
Help & FAQs
Classifications
Bioz

Biological Activity

제품 설명

M4K3233 is a selective ALK2 PROTAC degrader with a pDC₅₀ of 7.3 and a pIC₅₀ of 6.6. M4K3233 recruits CRBN to form a ternary complex with ALK2, mediating ALK2 degradation via the proteasomal and lysosomal pathways. M4K3233 induces moderate downregulation of RIPK2 and significant downregulation of SIK3 in mammalian cells. M4K3233 is applicable to research related to glioblastoma^[1]. (Pink: ALK2 ligand (HY-149591); Blue: Cereblon ligand (HY-14658); Black: linker).

In Vitro

M4K3233 (1 μM; 24 h) is a selective ALK2 degrader in ALK2-overexpressing HEK-293 cells and U87-MG glioblastoma cells, significantly reducing ALK2 levels alongside a small set of off-target proteins including PDE6D, FIZ1, SIK3, and RIPK2, while sparing most other kinases^[1].
M4K3233 (serial dilutions; 4 h) promotes ternary complex formation between ALK2 and CRBN in HEK-293 cells with an apparent pEC₅₀ of 7.42, as measured by a NanoBRET PPI assay^[1].
M4K3233 (0.0002-30 μM; 8 days) inhibits proliferation of patient-derived PDHGG cell lines with GI₅₀ values from 0.3 μM to 5 μM, but this effect appears independent of CRBN-mediated ALK2 degradation^[1].
M4K3233 (0.0002-30 μM; 4 days) reduces viability of U87-MG glioblastoma cells, but this cytotoxic effect is independent of CRBN-mediated ALK2 degradation^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Western Blot Analysis^[1]

Cell Line:

ALK2-HiBiT transfected HEK-293 cells
Concentration:

1 μM (M4K3233, 24 h incubation); 20 μM pomalidomide (20 min pretreatment); 20 μM M4K2009 (20 min pretreatment); 1 μM MG132 (20 min pretreatment); 1 μM bafilomycin A1 (20 min pretreatment)
Incubation Time:

24 h (M4K3233 treatment); 20 min (pretreatments)
Result:

Blocked ALK2 degradation when cells were pretreated with either pomalidomide or M4K2009, confirming reliance on both ALK2 and CRBN binding.
Partially recovered ALK2 levels when cells were pretreated with either MG132 or bafilomycin A1, while combined pretreatment with both inhibitors completely blocked ALK2 degradation.

Chemical Information

분자량 772.89
화학식 C₄₄H₄₈N₆O₇
SMILES

CC1=C(C2=CC=C(N3CCN(CC4CCN(C5=CC=C(C(N(C6CCC(NC6=O)=O)C7=O)=O)C7=C5)CC4)CC3)C=C2)C=NC=C1C8=CC(OC)=C(OC)C(OC)=C8
선적

Room temperature in continental US; may vary elsewhere.
보관

Please store the product under the recommended conditions in the Certificate of Analysis.

순도&문서

Handling Instructions (2659 KB)

References

[1]. Webb DT, et al. Targeting Activin Receptor-like Kinase 2 Using Heterobifunctional Protein Degraders. J Med Chem. 2026;69(9):11524-11546. [Content Brief]

Calculators

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Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

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Help & FAQs

How should lyophilized recombinant proteins be reconstituted and stored?

1. Before opening the cap, centrifuge the vial at 13000 rpm for 20-30 seconds. This step will ensure that any lyophilized powder that may have adhered to the cap or walls is collected at the bottom of the vial, minimizing the risk of product loss.

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MOQ

Minimum order quantity

100 mg

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