Selective enhancement of the interneuron network and gamma-band power via GluN2C/GluN2D NMDA receptor potentiation.

N-Methyl-d-aspartate receptors (NMDARs) are a family of ligand-gated ionotropic glutamate receptors that mediate a slow, calcium-permeable component to excitatory neurotransmission. The GluN2D subunit is enriched in GABAergic inhibitory interneurons in cortical tissue. Diminished levels of GABAergic inhibition contribute to multiple neuropsychiatric conditions, suggesting that enhancing inhibition might have therapeutic utility, thus making GluN2D modulation an attractive drug target.

Thienopyrimidinone Derivatives as a GluN2B/C/D Biased, Positive Allosteric Modulator of the -Methyl-d-Aspartate Receptor.

Positive allosteric modulators (PAMs) of the -methyl-d-aspartate receptor (NMDAR) have been proposed as therapeutics in several neuropsychiatric indications, including schizophrenia, depression, cognitive dysfunction, and anxiety. In particular, GluN2D-containing NMDARs are highly expressed in inhibitory interneurons and are a target of interest for drug development. Toward that end, we describe our investigation into the GluN2-selective EU 1622 series of PAMs that enhance receptor efficacy, increase agonist potency, prolong deactivation time course, reduce single channel conductance, and limit calcium influx.

Complete Genome Classification System of : An Updated Analysis.

is the major causative agent of acute gastroenteritis in both children under the age of 5 and young mammals and birds globally. RVAs are non-enveloped viruses with a genome comprising 11 double-stranded RNA segments. In 2008, the Rotavirus Classification Working Group pioneered a comprehensive and complete RVA genome classification system, establishing a specific threshold, which measures the genetic distances between homologous genes.

Structural basis for channel gating and blockade in tri-heteromeric GluN1-2B-2D NMDA receptor.

Discrete activation of N-methyl-D-aspartate receptor (NMDAR) subtypes by glutamate and the co-agonist glycine is fundamental to neuroplasticity. A distinct variant, the tri-heteromeric receptor, comprising glycine-binding GluN1 and two types of glutamate-binding GluN2 subunits, exhibits unique pharmacological characteristics, notably enhanced sensitivity to the anti-depressant channel blocker S-(+)-ketamine. Despite its significance, the structural mechanisms underlying ligand gating and channel blockade of tri-heteromeric NMDARs remain poorly understood.

Small molecule and peptide CXCR4 antagonists. A patent review from 2019 to 2024.

Introduction: The chemokine receptor CXCR4 has been under intense study due to the central role it plays in immune system regulation and the pathology of human disease. Although the first CXCR4 drug plerixafor emerged over a decade ago (2007), recently the first peptide (motixafortide, 2023) and the first oral small molecule (mavorixafor, 2024) CXCR4 antagonists became FDA approved.

Areas Covered: This article describes patent documents published during the period of 2019 through 2024 for both small molecule and peptides.