NP10679

NP10679 is a selective, pH dependent GluN2B subunit-specific N-methyl-D-aspartate (NMDA) receptor inhibitor with high oral bioavailability and good brain penetration. NP10679 inhibits GluN2B with IC50s of 23 and 142 nM at pH 6.9 and 7.6, respectively. NP10679 is a histamine H1 antagonist and a hERG channel inhibitor with IC50s of 73 and 620 nM, respectively. NP10679 is a reversible inhibitor of human liver CYP enzymes.

NP10679 (1-1000 nM) shows pH-dependently effects to GluN2B with IC₅₀s of 23 and 142 nM at pH 6.9 and 7.6, respectively^[2].
NP10679 shows functional inhibition to 5-HT2A, α adrenergic receptor-1A (α1A), H1-histamine receptor (H1) and hERG channel with IC₅₀ values of 1.71, 0.154, 0.073 and 0.617 μM, respectively^[2].
NP10679 shows K_i values of 2.29, 0.638, 1.92, 0.603, 1.92, 0.495, 3.09, 0.040 and 0.135 for 5-HT1D, 5-HT2A, 5-HT2B, α1A, α1B, α1D, α2C, H1 and serotonin transporter SERT^[2].

NP10679 (2, 5 and 10 mg/kg; i.p., prior to transient ischemia) reduces infarct volumes of transient ischemia mice^[2].

References:
[1]. Zaczek R, et al. Phase 1 Clinical Results for NP10679, a pH-sensitive GluN2B-selective N-methyl-d-aspartate Receptor Inhibitor. Clin Pharmacol Drug Dev. 2023 Jan 15.
[2]. Myers SJ, et al. A Glutamate N-Methyl-d-Aspartate (NMDA) Receptor Subunit 2B-Selective Inhibitor of NMDA Receptor Function with Enhanced Potency at Acidic pH and Oral Bioavailability for Clinical Use. J Pharmacol Exp Ther. 2021 Oct;379(1):41-52.