JNJ-64326067
JNJ-64326067 is an aggregated tau-binding agent with blood-brain barrier permeability, with a Ki of 2.4 nM. JNJ-64326067 selectively binds to aggregated tau protein but does not bind to aggregated β-amyloid protein, and shows no significant off-target binding to the tested receptors, ion channels, transporters, kinases or monoamine oxidases. JNJ-64326067 is applicable to the research of Alzheimer's disease.
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- No. CAS: 2173357-28-1
- Fòrmula: C15H12FN3
- Peso molecular:253.28
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Almacenamiento:
Please store the product under the recommended conditions in the Certificate of Analysis.
Actividad biológica
Descripciòn
In Vitro
[3H]JNJ-64326067 and [18F]JNJ-64326067 specifically bind to tau pathologies in post-mortem human AD brain sections, but do not bind to pathologies with only Aβ present, and this binding can be selectively blocked by non-radioactive JNJ-64326067[1].
JNJ-64326067 possesses physicochemical properties suitable for central nervous system penetration, exhibits no significant MDR1-mediated efflux, has a low free fraction in plasma and brain tissue, and shows high intrinsic clearance in rat, monkey and human liver microsomes as well as hepatocytes[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
Parmacokinetics
| Species | Dose | Route | CL | T1/2 | AUC | Vdss |
|---|---|---|---|---|---|---|
| Rat[1] | 0.03 mg/kg | i.v. | 228 mL/min/kg | 0.08 h | 2.2 ng·h/mL | 1.6 L/kg |
In Vivo
JNJ-64326067 (1-10 mg/kg; s.c.; i.v.; single dose) shows high initial brain uptake, rapid washout, and no detectable off-target binding in healthy female Wistar rats, with bone uptake indicating in vivo defluorination[1].
JNJ-64326067 (1 mg/kg; i.v.; single dose; simultaneous with [18F]9 injection) exhibits high brain uptake, rapid washout, homogeneous brain distribution, and no bone uptake in healthy male rhesus monkeys, with a blocking study showing increased peak uptake due to enhanced tracer availability for brain entry[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Sprague-Dawley (male)[1]
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Dosage:0.03 mg/kg
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Administration:i.v.; single dose
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Result:Exhibited a plasma clearance of 228 mL/min/kg.
Showed a plasma half-life of 0.08 h.
Reached a plasma AUC of 2.2 ng·h/mL.
Reached a cortex AUC of 8.72 ng·h/mL.
Had a volume of distribution at steady state (Vd,ss) of 1.6 L/kg.
Achieved a cortex-to-plasma ratio (Kp) of 4.0.
Had an estimated unbound brain-to-plasma ratio (Kp,uu) of 1.1.
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Animal Model:Wistar (female)[1]
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Dosage:10 mg/kg (pretreatment); 1 mg/kg (displacement)
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Administration:s.c.; single dose, 60 minutes pre [18F]9 injection; i.v.; single dose, 30 minutes post [18F]9 injection
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Result:Showed high initial brain uptake (SUV of 2.4 at 1 minute post-injection).
Underwent rapid brain washout (SUV of 0.2 at 60 minutes post-injection).
Did not reduce time-activity curve intensity with pretreatment and displacement, indicating no reversible or irreversible off-target specific binding.
Caused bone uptake at later time points, suggesting in vivo defluorination.
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Animal Model:male[1]
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Dosage:1 mg/kg
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Administration:i.v.; single dose; simultaneous with [18F]9 injection
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Result:Showed high brain uptake (SUV of 5.4 in whole brain, time to peak uptake: 4.5 minutes) with rapid washout.
Had homogeneous distribution across brain regions, with lower uptake in the corpus callosum and skull.
Showed no bone uptake up to 120 minutes post-injection.
Had a higher peak whole brain SUV of 7.5 in blocking study, with shorter time to peak (3.5 minutes) and slightly faster washout, and no pronounced blocking effect was observed.
Chemical Information
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No. CAS 2173357-28-1
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Peso molecular 253.28
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Fòrmula C15H12FN3
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SMILES
FC1=CC(=NC=C1C)NC=2C=CC=3C=NC=CC3C2
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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.
Protocolo
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Transepithelial/transendothelial electrical resistance assay
TEER measures electrical resistance across epithelial or endothelial monolayers cultured on permeable supports, and the readout reflects ionic conductance through the cell barrier, especially the paracellular pathway regulated by junctional integrity. TEER can be measured without destroying the monolayer and is commonly used before or during transport, permeability, barrier-disruption, and barrier-maturation experiments. TEER values are influenced by biological maturation and technical conditions; reported factors include temperature, medium formulation, passage number, electrode geometry, membrane properties, and junctional length during early monolayer maturation. Therefore, TEER should be interpreted with blank-insert subtraction, area normalization, repeated readings, and, when possible, orthogonal barrier readouts such as FITC-dextran flux or tight-junction staining.
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Amyloid: Congo Red Amyloid Staining
Congo red amyloid staining is a histochemical method used to detect extracellular amyloid deposits in tissue sections based on the affinity of Congo red dye for β-pleated sheet-rich protein aggregates. When bound to amyloid, Congo red produces characteristic apple-green birefringence under polarized light microscopy, which is widely regarded as a diagnostic feature of amyloid deposition in histopathology. The diagnostic principle relies on the combination of dye binding (congophilia) and optical anisotropy under polarized illumination, which distinguishes amyloid from most non-amyloid eosinophilic extracellular deposits in routine histological evaluation. Amyloid identification by Congo red staining remains a cornerstone in diagnostic pathology despite the availability of adjunct methods such as immunohistochemistry and mass spectrometry, particularly because of its ability to localize deposits directly within tissue architecture. The specificity of Congo red-positive deposits is incre
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Alzheimer’s Disease Modeling
Alzheimer’s Disease (AD) is a neurodegenerative disorder characterized by a progressive decline in cognitive functions and loss of specific types of neurons and synapses. Alzheimer's symptoms can be simulated in mice by injecting drugs (such as Aβ) or genetically modified.
Pureza y Documentación
Referencias
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)