2. Neuronal Signaling
  3. Tau Protein
  4. 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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JNJ-64326067

JNJ-64326067 Chemical Structure

CAS No. : 2173357-28-1

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Based on 1 publication(s) in Google Scholar

JNJ-64326067 Related Antibodies

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Description

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[1].

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.

JNJ-64326067 Related Antibodies
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 (0.03 mg/kg; i.v.; single dose) exhibits fast plasma clearance, short plasma half-life, and good brain exposure in healthy male Sprague-Dawley rats, with a cortex-to-plasma ratio of 4.0[1].
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.

Animal Model: Sprague-Dawley (male)[1]
Dosage: 0.03 mg/kg
Administration: i.v.; single dose
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.
Animal Model: Wistar (female)[1]
Dosage: 10 mg/kg (pretreatment); 1 mg/kg (displacement)
Administration: s.c.; single dose, 60 minutes pre [18F]9 injection; i.v.; single dose, 30 minutes post [18F]9 injection
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.
Animal Model: male[1]
Dosage: 1 mg/kg
Administration: i.v.; single dose; simultaneous with [18F]9 injection
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.
Molecular Weight

253.28

Formula

C15H12FN3
CAS No.
SMILES

FC1=CC(=NC=C1C)NC=2C=CC=3C=NC=CC3C2
Shipping

Room temperature in continental US; may vary elsewhere.
Storage

Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
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JNJ-64326067 Related Classifications

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Keywords:

JNJ-643260672173357-28-1JNJ64326067JNJ 64326067Tau Proteintransportersreceptorskinasesion channelsalzheimer’s diseaseβ-amyloidblood-brain barriermonoamine oxidase enzymesrataggregated tau proteinInhibitorinhibitorinhibit

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