Brelgometon
Brelgometon (ATH-1105) is an orally active HGF/MET positive modulator. Brelgometon activates downstream ERK and AKT cascades. Brelgometon reduces pro-inflammatory cytokine levels and extranuclear TDP-43 aggregation; it also upregulates EAAT2 expression and improves mitochondrial function. Brelgometon protects neurons from excitotoxicity, inflammation, oxidative stress and mitochondrial dysfunction; it also maintains neurite length, neuromuscular junction integrity and sciatic nerve function. Brelgometon alleviates motor function deterioration, maintains body weight and prolongs survival in ALS transgenic mice. Brelgometon is applicable to research related to amyotrophic lateral sclerosis.
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- CAS No.: 3060541-19-4
- 화학식: C21H28F3N3O2
- 분자량:411.46
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보관:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
- 순도&문서
- References
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Help & FAQs
Biological Activity
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Met |
EAAT2 |
Brelgometon (1 pM-10 nM; 15 min) positively regulates HGF-mediated MET phosphorylation in HEK293 cells, with significant enhancement observed at concentrations of 10 pM and 100 pM[1].
Brelgometon (1 μM; 20 min) positively regulates HGF-dependent intracellular signaling pathways in HEK293 cells, and significantly enhances the phosphorylation levels of ERK and AKT at a concentration of 1 μM[1].
Brelgometon (pre-incubated for 15 minutes, followed by co-incubation with neurotoxic insults for 24 hours) exerts neuroprotective effects on primary rat cortical neurons and maintains cell viability against multiple ALS-related neurotoxic insults[1].
Brelgometon (100 pM-1 μM; 15 min) protects primary rat spinal motor neurons from glutamate-induced excitotoxic injury, as evidenced by increased cell viability, preserved neurite structure, alleviated TDP-43 pathological changes, enhanced mitochondrial function, and inhibited caspase-3-mediated apoptosis[1].
Brelgometon (100 nM-1 μM; 23 h) exerts anti-inflammatory effects in LPS-activated BV2 microglia, reducing the production and gene expression of pro-inflammatory mediators[2].
Brelgometon (1 nM-1 μM; 20 min) protects rat primary motor neuron-astrocyte co-culture systems from glutamate-induced injury and ameliorates ALS-associated astrocyte dysfunction[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:HEK293 cells
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Concentration:1 pM, 10 pM, 100 pM, 1 nM, 10 nM
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Incubation Time:15 minutes
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Result:Increased MET phosphorylation significantly at 10 pM relative to 1 ng/mL HGF alone.
Increased MET phosphorylation significantly at 100 pM relative to 1 ng/mL HGF alone.
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Cell Line:human embryonic kidney 293 (HEK293) cells
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Concentration:1 pM, 10 pM, 100 pM, 1 nM, 10 nM (MET phosphorylation assay); 1 μM (ERK/AKT phosphorylation assay)
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Incubation Time:15 min (MET phosphorylation assay); 20 min (ERK/AKT phosphorylation assay)
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Result:Significantly increased MET phosphorylation at 10 pM and 100 pM compared with 1 ng/mL HGF alone.
Significantly increased phosphorylation of both ERK and AKT at 1 μM compared with controls treated with 2 ng/mL HGF alone.
| Species | Dose | Route | Cmax | AUC0-inf | Tmax | T1/2 |
|---|---|---|---|---|---|---|
| Mice[2] | 10 mg/kg | p.o. | 652 ng/mL | 611 ng·h/mL | 0.17 h | 0.78 h |
Brelgometon (10-20 mg/kg; daily; 2 months) dose-dependently preserves body weight, motor and nerve function, reduces inflammation and neurodegeneration biomarkers, and attenuates sciatic nerve pathology in Prp-TDP43A315T ALS mice, with the 20 mg/kg dose yielding the most robust effects[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:TDP-43A315T hemizygous transgenic mice (male, 1-month-old, ALS model)[1]
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Dosage:0.4 mg/kg; 2 mg/kg; 10 mg/kg
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Administration:p.o.; daily; 2 months
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Result:Increased average body weight at 10 and 11 weeks of age in mice treated with 2 mg/kg; increased average body weight at 9, 10, and 11 weeks of age in mice treated with 10 mg/kg, compared to vehicle-treated ALS mice.
Improved cross time after 1 and 2 months of treatment in the balance beam test with 10 mg/kg treatment.
Increased latency to fall after 2 months of treatment in the rotarod test with 2 mg/kg and 10 mg/kg treatments.
Improved grip strength after 1 and 2 months of treatment with 10 mg/kg treatment; improved grip strength after 2 months of treatment with 2 mg/kg treatment.
Increased latency to fall after 2 months of treatment in the Kondziela screen test with 2 mg/kg treatment; increased latency to fall after 1 and 2 months of treatment in the Kondziela screen test with 10 mg/kg treatment.
Increased compound muscle action potential (CMAP) amplitude after 1 and 2 months of treatment with 2 mg/kg and 10 mg/kg treatments.
Increased nerve conduction velocity (NCV) after 2 months of treatment with 2 mg/kg treatment; increased NCV after 1 and 2 months of treatment with 10 mg/kg treatment.
Decreased plasma tumor necrosis factor α (TNF-α) concentrations after 1 month of treatment with all three doses; decreased plasma TNF-α concentrations after 2 months of treatment with 2 mg/kg and 10 mg/kg doses.
Decreased plasma interleukin 6 (IL-6) concentrations after 1 month of treatment with 2 mg/kg and 10 mg/kg doses; decreased plasma IL-6 concentrations after 2 months of treatment with all three doses.
Decreased plasma neurofilament light chain (NfL) concentrations after 1 and 2 months of treatment with all three doses.
Increased the number of axons per area after 2 months of treatment with 2 mg/kg and 10 mg/kg treatments.
Increased mean axonal diameter after 2 months of treatment with all three doses; preserved large-diameter axons, resulting in an axon diameter distribution similar to wild-type mice.
Yielded lower g-ratios after 2 months of treatment with all three doses, normalizing the relationship between axon diameter and relative myelin thickness.
Chemical Information
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CAS No. 3060541-19-4
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분자량 411.46
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화학식 C21H28F3N3O2
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SMILES
C[C@@H](C(N(C1)C[C@@H](C)CC)=O)N(C(CC2)=O)C1N2CC3=CC=C(C=C3)C(F)(F)F
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Synonyms
ATH-1105
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선적
Room temperature in continental US; may vary elsewhere.
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보관
Please store the product under the recommended conditions in the Certificate of Analysis.
순도&문서
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Brelgometon Related Classifications
HY-187892 Related Classifications
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