JNJ-3792165 is a potent and selective antagonist at GPR139, a non-canonical opioid receptor. It has high affinity for human GPR139 (pKi = 7.7, displacement of [3H] JNJ-6353054) and behaves as an antagonist in a [35S]GTPgammaS assay (pKb = 7.4) and calcium mobilization assay.1 It displayed no significant affinity in a selectivity screen of over 50 other neurotransmitter and neuropeptide receptors (less than 50% inhibition at 1 µM).1 Completely blocks (10 mM) the effects of optogenetic stimulation of dynorphin release in dynorphinergic neurons of the nucleus accumbens at 10 mM.2 JNJ-3792165 is an important new tool for exploring the biology of GPR139.3,4
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