nmdar 1

NMDAR antagonist 1 is an orally active, NR2B-selective NMDAR antagonist.

NMDAR HDAC-IN-1 (Compound 9d) is a potent dual inhibitor of N-methyl-D-aspartate receptors (NMDARs) and histone deacetylases (HDACs), with a high affinity for NMDARs (Ki = 0.59 μM) and significant inhibitory effects on various HDAC isoforms, including HDAC1, HDAC2, HDAC3, HDAC6, and HDAC8 with IC50 values of 2.67 μM, 8.00 μM, 2.21 μM, 0.18 μM, and 0.62 μM, respectively; additionally, it efficiently crosses the blood-brain barrier [1].

(Rac)-NMDAR antagonist 1 is a racemate of NMDAR antagonist 1, a potent, orally active, NR2B-selective NMDAR antagonist.

GluN2B-NMDAR Antagonist-1, an orally active compound, functions as a GluN2B-NMDAR antagonist with neuroprotective properties. It is applicable in the research of ischemic injury [1].

1-[2,4-Dihydroxy-6-methoxy-3-(3-methyl-2-buten-1-yl)phenyl]-3-(4-hydroxyphenyl)-2-propen-1-one (Xanthohumol) , prenylchacone flavonoid, is a natural product with multi-biofunctions purified from Hops Humulus lupulus,is effective against HIV-1 and might serve as an interesting lead compound. It may represent a novel chemotherapeutic agent for HIV-1 infection.

Tat-NR2B9c acetate (NA-1 acetate) is a postsynaptic density-95 (PSD-95) inhibitor, with EC50 values of 6.7 nM and 670 nM for PSD-95d2 (PSD-95 PDZ domain 2) and PSD-95d1, respectively. Tat-NR2B9c acetate disrupts the PSD-95/NMDAR interaction, inhibiting NR2A and NR2B binding to PSD-95 with IC50 values of 0.5 μM and 8 μM, respectively. Tat-NR2B9c acetate also inhibits neuronal nitric oxide synthase (nNOS)/PSD-95 interaction, and possesses neuroprotective efficacy.

HINT1-IN-1 (compound 8) is an inhibitor of histidine triad nucleotide-binding protein 1 (HINT1) with a Ki of 1.14 μM. It influences the cross-regulation between μ-opioid receptors (MOR) and NMDA receptors (NMDAR).

MDAR IN-1 (Compound 5m) is a brain-penetrant acetylcholinesterase (AChE) inhibitor and an antagonist of the NMDAR receptor GluN1/GluN2B subtype. It effectively inhibits AChE activity, enhances cholinergic neurotransmission, and blocks NMDAR to reduce excitotoxicity. MDAR IN-1 shows potential for Alzheimer’s disease research.

Tat-NR2BAA is an inactive control peptide of Tat-NR2B9c. It shares a similar sequence with Tat-NR2B9c, but possesses a double-point mutation in the COOH terminal tSXV motif. This mutation renders Tat-NR2BAA unable to bind PSD-95. Tat-NR2B9c, on the other hand, is a membrane-permeable peptide that interferes with PSD-95 NMDAR binding. This interference leads to the decoupling of NR2B- and or NR2A-type NMDARs from PSD-95[1][2].

NMDA receptor antagonist 4 (IIc) is an uncompetitive, voltage-dependent, orally active NMDAR blocker with an IC50 of 1.93 μM. It shows positive predicted blood-brain-barrier (BBB) permeability and can be used in Alzheimer's disease research[1].

Withaphysalin D, isolated from water lilies, is a selective antagonist for the N-methyl-D-aspartate receptor (NMDAR) containing GluN2B with neuroprotective properties. This compound is capable of crossing the blood-brain barrier [1].

Tat-NR2BAA TFA serves as the inactive control peptide for Tat-NR2B9c, featuring a comparable sequence with a crucial distinction: a double-point mutation in its COOH-terminal tSXV motif. This alteration renders Tat-NR2BAA TFA unable to bind to PSD-95, in contrast to Tat-NR2B9c. The latter is a membrane-permeant peptide that impedes PSD-95 NMDAR interaction, specifically detaching NR2B- and or NR2A-type NMDARs from PSD-95 [1].

Neurogranin (48-76), mouse, is a peptide comprising residues 48-76 of Neurogranin, a post-synaptically exclusive calmodulin-binding protein that mediates NMDAR-driven synaptic plasticity by regulating the calcium-calmodulin (Ca2+-CaM) pathway [1].

VSGLNPSLWSIFGLQFILLWLVSGSRHYLW, a 30-amino-acid peptide, mirrors the C-terminal domain of α2δ-1 and is recognized as the α2δ-1Tat peptide. It disrupts the α2δ-1 - NMDAR interaction both in vitro and in vivo, offering a potential research tool for neuropathic pain studies [1].

VSGLNPSLWSIFGLQFILLWLVSGSRHYLW (TFA), a 30-amino-acid peptide, mimics the C-terminal domain of α2δ-1, known as α2δ-1Tat peptide. This compound disrupts the α2δ-1 - NMDAR interaction both in vitro and in vivo, demonstrating potential utility in neuropathic pain research [1].

DQP-26, a potent negative allosteric modulator of NMDA receptors (NMDARs), exhibits IC50 values of 0.77 μM for GluN2C and 0.44 μM for GluN2D subunits, indicating potential application in research on NMDAR-associated neurological diseases [1].

6-Hydroxykynurenic acid (6-HKA), a kynurenic acid (KYNA) derivative isolated from Ginkgo leaves, functions as a low-affinity NMDAR antagonist with an IC50 of 59 μM [1].

TAT-GluN2BCTM is a membrane-permeable peptide that selectively targets active DAPK1 (Death-associated protein kinase 1) for lysosomal degradation, protecting neurons against oxidative stress and NMDAR-mediated excitotoxicity, making it valuable for neuroprotection research studies [1].

GluN1 (359-378), an antibody targeting the N-methyl-D-aspartate receptor (NMDAR), can cross the blood-brain barrier and is used in research on immune-based therapies for anti-NMDAR encephalitis [1].

GluN1 (356-385) is an antigenic peptide implicated in N-methyl-D-aspartate receptor (NMDAR) encephalitis, shown to decrease NMDAR surface cluster density in hippocampal neurons, and serves as a tool to investigate the pathogenesis of anti-NMDAR encephalitis [1].

Dihydroquinoline-pyrazoline DQP-997-74 (compound 2i) is a selective N-methyl-d-aspartate receptor (NMDAR) inhibitor that preferentially targets GluN2C D subunits, with IC50 values of 0.069 μM and 0.035 μM, respectively, and possesses blood-brain barrier permeability. It enhances its inhibitory potency in a time-dependent manner when combined with the agonist glutamate, reducing epileptogenic events in a murine model of tuberous sclerosis complex (TSC)-induced epilepsy. DQP-997-74 is potentially applicable for the study of NMDAR-related neurological diseases [1].

Compound I-52 (AChE-IN-53) is a potent inhibitor of NMDAR, exhibiting favorable behavioral and neuroprotective effects [1].