Information
JNJ 31020028 JNJ 31020028 is a novel neuropeptide Y Y2 receptor antagonist which bound with high affinity with human and rat Y2 receptor (pIC50=8.07±0.05 for human Y2 receptor, and pIC50=8.22±0.06 for rat Y2 receptor) and >100-fold selective versus human Y1, Y4, and Y5 receptors.
Targets
rat Y2 receptor ; human Y2 receptor 8.22(pIC50); 8.07(pIC50)
In vitro
JNJ-31020028 is assayed by binding in a panel of 50 receptors, ion channels, and transporters assays including adenosine (A1, A2A, A3), adrenergic (α1, α2, β1), angiotensin (AT1), dopamine (D1, D2), bradykinin (B2), cholecystokinin (CCKA), galanin (GAL2), melatonin (ML1), muscarinic (M1, M2, M3), neurotensin (NT1), neurokinin (NK2, NK3), opiate (μ, κ, δ), serotonin (5-HT1A, 5-HT1B, 5-HT2A, 5-HT3, 5-HT5A, 5-HT6, 5-HT7), somatostatin, Vasotocin (V1a), norepinephrine transporter, dopamine transporter, and ion channels (sodium, calcium, potassium, and chloride). The Y2 antagonist at concentrations up to 10μM has no significant affinity for any receptor/transporter/ion channel (<50% inhibition at 10μM) other than the Y2 receptor. Selectivity of Y2 antagonist is further evaluated in a panel comprised of 65 kinases. JNJ-31020028 (10μM) does not inhibit any of the kinase included in the panel.
In vivo
In a variety of anxiety models, JNJ-31020028 is found to be ineffective, although it does block stress-induced elevations in plasma corticosterone, without altering basal levels, and normalized food intake in stressed animals without affecting basal food intake. JNJ-31020028 is administered to rats by the oral (10 mg/kg), intravenous (1 mg/kg), and subcutaneous (10 mg/kg) route, and pharmacokinetic parameters are determined. The compound has poor oral bioavailability (6%) but high subcutaneous bioavailability (100%). Subcutaneous dosing is the preferred route for several of the models and yields good plasma levels (Cmax 4.35 μmol/l) and fast absorption with a 0.83-h half-life. JNJ-31020028 has no significant effect on locomotor activity during the test.
C23081494