PROTAC MLKL Degrader-3
PROTAC MLKL Degrader-3 is a MLKL PROTAC degrader with DC50 values of 248.9 nM (Hepa1-6) and 271.3 nM (HepG2), respectively. PROTAC MLKL Degrader-3 induces proteasome- and cereblon-dependent MLKL degradation via ubiquitination. PROTAC MLKL Degrader-3 reduces intratumoral MLKL levels and inhibits tumor growth in mice. PROTAC MLKL Degrader-3 can be used in the research of hepatocellular carcinoma.
(Pink: Mixed Lineage Kinase ligand (HY-182344); Blue: Cereblon ligand (HY-14658); Black: linker).
For research use only. We do not sell to patients.
- Formula: C49H47F4N11O8S
- Molecular Weight:1026.02
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biological Activity
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Chemical Information
- Purity & Documentation
- References
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Biological Activity
PROTAC MLKL Degrader-3 (compound C116) (1 nM-20000 nM, 0.5 μM-1 μM; 2 h-96 h) potently and rapidly degrades MLKL in murine Hepa1-6 and human HepG2 HCC cells, with DC50 values of 248.9 nM and 271.3 nM respectively, and maximal degradation exceeding 90% for both cell lines[1].
PROTAC MLKL Degrader-3 (C116) (1 μM; 4 h) selectively degrades MLKL in murine Hepa1-6 HCC cells without significantly affecting other proteins in the proteome[1].
PROTAC MLKL Degrader-3 (C116) (6 h) mediates MLKL degradation in a proteasome- and CRBN-dependent manner via enhancing MLKL ubiquitination in murine Hepa1-6 and human HEK293T cells[1].
PROTAC MLKL Degrader-3 (C116) (1 μM-10 μM; 24 h pretreatment, followed by 20 h PA stimulation) potentiates PA-induced parthanatos and subsequent cytotoxicity in murine Hepa1-6 and human HepG2 HCC cells, with this effect dependent on parthanatos signaling[1].
PROTAC MLKL Degrader-3 (C116) degrades MLKL across diverse murine and human cancer cell lines, including colorectal, triple-negative breast, and lung cancer cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:murine Hepa1-6 HCC cells, human HepG2 HCC cells
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Concentration:1 μM, 10 μM (24 h); 1 nM-20000 nM (24 h); 0.5 μM, 1 μM (2 h, 4 h, 6 h, 12 h, 24 h, 48 h, 72 h, 96 h)
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Incubation Time:24 h (1 μM, 10 μM, 1 nM-20000 nM); 2 h-96 h (0.5 μM, 1 μM)
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Result:Reduced MLKL levels to 9.6% in Hepa1-6 cells and 18.7% in HepG2 cells at 1 μM for 24 h.
Reduced MLKL levels to 2.5% in Hepa1-6 cells and 11.7% in HepG2 cells at 10 μM for 24 h.
Induced concentration-dependent degradation with DC50 values of 248.9 nM in Hepa1-6 cells and 271.3 nM in HepG2 cells, and maximal percent degradation (Dₘₐₓ) of 99.3% in Hepa1-6 cells and 91.2% in HepG2 cells.
Induced over 90% MLKL reduction as early as 2 h at 1 μM, with robust degradation maintained for 48 h and recovery observed by 96 h.
| Species | Dose | Route | T1/2 | AUC |
|---|---|---|---|---|
| Mice[1] | 10 mg/kg | i.p. | 5.5 h | 1519 ng·h/mL |
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6 (male, 5 weeks old, orthotopic liver tumor model via surgical implantation of Hepa1−6-luc cells)[1]
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Dosage:10 mg/kg
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Administration:i.p.; daily; study duration
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Result:Significantly inhibited orthotopic HCC tumor growth, as measured by reduced total bioluminescent flux.
Significantly reduced intratumoral MLKL levels in treated mice.
Showed good tolerability, with no induced weight loss in treated mice.
Chemical Information
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Molecular Weight 1026.02
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Formula C49H47F4N11O8S
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SMILES
NC1=C(C2=C(C=N1)C3=CN(N=C3)C4CCN(CC4)C(C5CCN(C6=CC=C(C(N(C7C(NC(CC7)=O)=O)C8=O)=O)C8=C6)CC5)=O)C(C9=CC(OC(C%10=CC=C(C=C%10)F)C)=C(C=C9F)NS(=O)(C(F)F)=O)=NN2C
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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)
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