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JNJ-54175446 

Cat. No. M28720
JNJ-54175446  Structure
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Biological Activity

JNJ-54175446 is a potent and selective brain penetrant P2X7 receptor antagonist, with pIC50s of 8.46 and 8.81 for hP2X7 receptor and rP2X7 receptor, respectively.

Chemical Information
Molecular Weight 440.78
Formula C18H13ClF4N6O
CAS Number 1627902-21-9
Form Solid
Solubility (25°C) DMSO 62.5 mg/mL (ultrasonic)
Storage Powder          -20°C   3 years ;  4°C   2 years
In solvent       -80°C   6 months ;  -20°C   1 month
Conversion of different model animals based on BSA (PMID: 27057123)
Species Mouse Rat Rabbit Guinea pig Hamster Dog
Weight (kg) 0.02 0.15 1.8 0.4 0.08 10
Body Surface Area (m2) 0.007 0.025 0.15 0.05 0.02 0.5
Km factor 3 6 12 8 5 20
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.

References

[1] Kasper Recourt, et al. J Psychopharmacol. Characterisation of the pharmacodynamic effects of the P2X7 receptor antagonist JNJ-54175446 using an oral dexamphetamine challenge model in healthy males in a randomised, double-blind, placebo-controlled, multiple ascending dose trial

[2] Yan Xu, et al. Clin Transl Sci. Translational Model-Informed Dose Selection for a Human Positron Emission Tomography Imaging Study of JNJ-54175446, a P2X7 Receptor Antagonist

[3] Hartmuth C Kolb, et al. J Nucl Med. Preclinical Evaluation and Nonhuman Primate Receptor Occupancy Study of 18F-JNJ-64413739, a PET Radioligand for P2X7 Receptors

[4] Michel Koole, et al. J Nucl Med. 18F-JNJ-64413739, a Novel PET Ligand for the P2X7 Ion Channel: Radiation Dosimetry, Kinetic Modeling, Test-Retest Variability, and Occupancy of the P2X7 Antagonist JNJ-54175446

[5] Maarten Timmers, et al. J Psychopharmacol. Clinical pharmacokinetics, pharmacodynamics, safety, and tolerability of JNJ-54175446, a brain permeable P2X7 antagonist, in a randomised single-ascending dose study in healthy participants

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