ML 2-23
ML 2-23 is a PROTAC degrader that recruits RNF114 to target BCR-ABL/c-ABL for degradation. ML 2-23 promotes proteasome-dependent degradation of the target protein and inhibits phosphorylation of downstream CRKL. At concentrations used for BCR-ABL degradation, ML 2-23 only causes slight impairment to the viability of cancer cells. ML 2-23 can be used in the research of chronic myeloid leukemia.
(Pink: Bcr-Abl Target protein ligand; Blue: RNF114 ligand (HY-28328); Black: linker).
For research use only. We do not sell to patients.
- Formula: C47H53BrCl2N10O7S
- Molecular Weight:1052.86
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
All PROTACs Isoforms
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Biological Activity
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BCR-ABL |
c-ABL |
ML 2-23 (0.01-5 μM; 16 h) reduces the protein levels of BCR-ABL and c-ABL in K562 cells in a concentration-dependent manner, with a stronger degradation effect on BCR-ABL than on c-ABL, while simultaneously decreasing the phosphorylation of CRKL, a downstream substrate of BCR-ABL. It only slightly reduces the viability of K562 cells in WST assays, indicating that the observed protein reduction is not caused by general cytotoxicity under the concentration and treatment time used to evaluate BCR-ABL degradation[1].
Pretreatment with ML 2-23 (1 μM; 12 h; 30 min pretreatment with 5 μM MG132 (HY-13259)) significantly reverses the ML 2-23-induced degradation of BCR-ABL and c-ABL in K562 cells, indicating that this degradation is proteasome-dependent[1].
ML 2-23 (5 μM; 16 h) does not significantly affect BCR-ABL mRNA levels in K562 cells, but increases c-ABL mRNA levels, indicating that the reduction in BCR-ABL and c-ABL proteins is not caused by transcriptional downregulation[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:K562 chronic myeloid leukemia cells
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Concentration:0.01, 0.1, 0.5, 1, 5 μM
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Incubation Time:16 h
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Result:Concentration-dependently reduced BCR-ABL and c-ABL protein levels, preferentially degraded BCR-ABL over c-ABL, and decreased p-CRKL levels.
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Cell Line:K562 chronic myeloid leukemia cells
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Concentration:MG132: 5 μM; 1 μM
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Incubation Time:MG132 pretreatment for 30 min; ML 2-23 treatment for 12 h
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Result:Reduced BCR-ABL and c-ABL protein levels; MG132 pretreatment significantly rescued the degradation.
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Cell Line:K562 chronic myeloid leukemia cells
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Concentration:5 μM
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Incubation Time:16 h
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Result:Did not significantly alter BCR-ABL mRNA levels but increased c-ABL mRNA levels.
Chemical Information
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Molecular Weight 1052.86
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Formula C47H53BrCl2N10O7S
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SMILES
O=C(COC1=CC=C(C2CC(C3=CC=C(Br)C=C3)=NN2C(CCl)=O)C=C1)NCCOCCOCCOCCN4CCN(C5=NC(C)=NC(NC6=NC=C(C(NC7=C(C)C=CC=C7Cl)=O)S6)=C5)CC4
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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)