MH-06
MH-06 is an orally active 12-lipoxygenase (ALOX12) PROTAC degrader. MH-06 specifically binds to ALOX12 and recruits E3 ubiquitin ligase to mediate ubiquitination and degradation of the target protein. MH-06 inhibits the MAPK signaling pathway, reduces the production of reactive oxygen species (ROS), restores mitochondrial function, regulates macrophage polarization and decreases the release of pro-inflammatory cytokines. MH-06 can be used for the research of acute pancreatitis.
(Pink: 12-LOX ligand (HY-187183); Blue: Cereblon ligand (HY-10984); Black: linker).
Para uso exclusivo en investigación. No vendemos a pacientes.
- Fòrmula: C30H27N7O7
- Peso molecular:597.58
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Almacenamiento:
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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Actividad biológica
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Chemical Information
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Actividad biológica
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12-LOX |
Cereblon |
MH-06 (1.25-20.0 μM; 24 h) dose-dependently degrades ALOX12 protein in LPS (HY-D1056)-induced inflammatory AR42J rat pancreatic exocrine cells[1].
MH-06 (10.0 μM; 24 h) significantly reduces intracellular 12-HETE production in LPS-induced inflammatory AR42J rat pancreatic exocrine cells[1].
MH-06 (10.0 μM; 24 h) significantly reduces the transcription levels of pro-inflammatory factors TNF-α, IL-6 and chemokine CCL2 in LPS-induced inflammatory AR42J rat pancreatic exocrine cells[1].
MH-06 (5.0-10.0 μM; 24 h) reduces LPS-induced reactive oxygen species (ROS) production in inflammatory AR42J rat pancreatic exocrine cells in a dose-dependent manner, with the ROS level in the 10.0 μM MH-06 treatment group being 65.4% lower than that in the LPS-induced control group[1].
MH-06 (5.0-10.0 μM; 24 h) dose-dependently restores the mitochondrial membrane potential of LPS-induced inflammatory AR42J rat pancreatic exocrine cells and improves mitochondrial function[1].
MH-06 (5.0-10.0 μM; 24 h) dose-dependently inhibits the phosphorylation-dependent activation of the ERK and P38 branches of the MAPK signaling pathway in LPS-induced inflammatory AR42J rat pancreatic exocrine cells, without affecting the total ERK or P38 protein levels[1].
MH-06 (5.0-10.0 μM; 24 h) dose-dependently reduces the protein expression levels of pyroptosis markers Caspase-1, NLRP3 and ASC in LPS-induced inflammatory AR42J rat pancreatic exocrine cells[1].
MH-06 (treated at concentrations of 5.0-10.0 μM for 12 hours following 24-hour LPS stimulation) dose-dependently regulates LPS-stimulated RAW264.7 murine macrophages by reducing M1 polarization and enhancing M2 polarization, while inhibiting the secretion of pro-inflammatory INF-γ[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:LPS-induced inflammatory AR42J rat pancreatic exocrine cells
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Concentration:1.25, 2.5, 5.0, 10.0, 15.0, 20.0 μM
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Incubation Time:24 h
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Result:Nearly achieved complete degradation of ALOX12 protein at 10.0 μM.
Showed significant degradation activity at 5.0 μM, with almost complete degradation occurring at 10.0 μM and higher concentrations.
Confirmed dose-dependent reduction in ALOX12 protein levels relative to β-actin.
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Cell Line:LPS-induced inflammatory AR42J rat pancreatic exocrine cells
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Concentration:10.0 μM
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Incubation Time:24 h
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Result:Significantly inhibited the transcriptional levels of TNF-α, IL-6, and CCL2 compared to the LPS-induced control group.
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Cell Line:LPS-induced inflammatory AR42J rat pancreatic exocrine cells
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Concentration:5.0, 10.0 μM
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Incubation Time:24 h
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Result:Had no significant effect on total ERK and P38 protein levels.
Significantly inhibited the expression of phosphorylated ERK (p-ERK) and phosphorylated P38 (p-P38) in a concentration-dependent manner, with higher concentrations showing greater inhibitory activity.\nSignificantly reduced the protein expression levels of Caspase-1, NLRP3, and ASC in a concentration-dependent manner.
Showed the strongest inhibitory effect at 10.0 μM.
Compared with single-dose administration, MH-06 (60 mg/kg; p.o.; administered twice) exerts superior preventive and therapeutic effects on caerulein-induced acute pancreatitis in C57BL/6J mice[1].
MH-06 (200-400 mg/kg; p.o.; single administration) shows good tolerance in C57BL/6J mice. With a single intragastric dose up to 400 mg/kg, no acute toxicity or adverse reactions are observed during the 7-day observation period[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6J mice (18-22 g, healthy)[1]
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Dosage:30 mg/kg; 60 mg/kg; 90 mg/kg
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Administration:p.o.; single dose
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Result:Reduced serum amylase, serum lipase, pancreatic trypsin activity, and pancreatic myeloperoxidase (MPO) activity in a dose-dependent manner.
Decreased serum amylase by 44.89%, serum lipase by 49.58%, pancreatic trypsin activity by 50.79%, and pancreatic MPO activity by 56.80% at 90 mg/kg compared to untreated cerulein-induced AP mice.
Alleviated pancreatic edema, inflammatory cell infiltration, and acinar cell necrosis in a dose-dependent manner, with the 90 mg/kg group showing the most significant improvement in pancreatic tissue damage.
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Animal Model:C57BL/6J mice (18-22 g, healthy)[1]
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Dosage:60 mg/kg
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Administration:p.o.; two doses: 1 hour pre-modeling and 6 hours post-final cerulein injection
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Result:Exerted a significantly stronger inhibitory effect on acute pancreatitis compared to the single intervention group, though its efficacy was slightly lower than that of the single 90 mg/kg MH-06 dose group.
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Animal Model:C57BL/6J mice (18-22 g, healthy)[1]
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Dosage:200 mg/kg; 300 mg/kg; 400 mg/kg
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Administration:p.o.; single dose
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Result:Showed no abnormal behavioral or physical manifestations in any dose group within 24 hours.
Maintained normal mental status, locomotor activity, food intake, and showed no significant body weight fluctuations over the 7-day observation period.
Chemical Information
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Peso molecular 597.58
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Fòrmula C30H27N7O7
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SMILES
O=C1CCC(C(N1)=O)N2C(C3=C(C(NC(CN4CCN(CC4)CC5=NC6=C(C(N5)=O)OC7=CC=CC=C76)=O)=CC=C3)C2=O)=O
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureza y Documentación
Referencias
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
MH-06 Related Classifications
HY-187182 Related Classifications
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