mGluR Modulator

Troriluzole, a third-generation, tripeptide proagent of Riluzole (HY-B0211), is an orally active glutamate modulator. Troriluzole reduces synaptic glutamate level and increases the synaptic glutamate absorption. Troriluzole has the potential for Alzheimer disease and generalized anxiety disorder (GAD).

BMS-984923, a potent mGluR5 silent allosteric modulator (SAM), with exquisite binding affinity (K_i = 0.6 nM), exhibits good oral bioavailability and BBB penetration. BMS-984923 potently inhibits the PrPC-mGluR5 interaction and prevents pathological Aβo signaling without affecting physiological glutamate signaling.

JNJ-46356479 is a selective and orally bioavailable mGlu2 receptor positive allosteric modulator (PAM), with the EC₅₀ of 78 nM. JNJ-46356479 shows active in vivo.

VU0155094 is a positive allosteric modulator with differential activity at the various group III mGluRs.

LSN2463359 is positive allosteric modulator of metabotropic glutamate 5 (mGlu₅). LSN2463359 attenuates aspects of the behavioral response to administration of the competitive NMDA receptor antagonist. LSN2463359 selectively attenuates reversal learning deficits observed in the neurodevelopmental MAM E17 model. LSN2463359 is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.

Raseglurant hydrochloride is a negative allosteric modulator of mGluR5. Raseglurant hydrochloride can be used in study migraine.

MNI137 is a potent and selective negative allosteric modulator for group II mGluRs. MNI137 has IC₅₀s values of 8.3 and 12.6 nM for human and rat mGlu2 inhibition of glutamate-induced calcium mobilization.

O-Phospho-L-serine-¹³C₃,¹⁵N is the ¹³C- and ¹⁵N-labeled O-Phospho-L-serine. O-Phospho-L-serine is the immediate precursor to L-serine in the serine synthesis pathway, and an agonist at the group III mGluR receptors (mGluR4, mGluR6, mGluR7, and mGluR8); O-Phospho-L-serine also acts as a weak antagonist for mGluR1 and a potent antagonist for mGluR2.

Raseglurant (ADX-10059) is a mGlu5 receptor negative allosteric modulator. Raseglurant is effective against migraine. Raseglurant reduces the Haloperidol (HY-14538)-induced catalepsy in mice.

Valiglurax (VU0652957) is a potent, orally active and selective mGlu4 positive allosteric modulator with EC₅₀ values of 64.6 nM and 197 nM for hmGlu₄/Gqi5 and rmGlu₄ GIRK, respectively. Valiglurax is a central nervous system (CNS) penetrant. Valiglurax can be used in research of Parkinson's disease.

PHCCC(4Me) (THCCC), a PHCCC analog, is a dual mGluR2 (IC₅₀ of 1.5 μM) negative allosteric modulator and mGluR3 (EC₅₀ of 8.9 μM) positive allosteric modulator.

mGluR3 modulator-1 (compound 3) is a mGluR3 modulator, with an EC₅₀ of 1-10 μM in HEK293T-mGluR-Gqi5 Calcium Mobilization Assay.

mG2N001 is a negative allosteric modulator (NAM) (IC₅₀: 93 nM) of the metabotropic glutamate receptor mGluR2 and binds to mGluR2 as an antagonist (Ki: 63 nM). mG2N001 is microparticle- and plasma-stable, and its radioisotope ^[11C]mG2N001 can be used in PET imaging. ^[11C]mG2N001 has good brain heterogeneity and brain penetration, and can selectively accumulate in mGluR2-rich regions, producing high-contrast brain images.

VU 0360223 is a potent metabotropic glutamate receptors (mGluR) negative allosteric modulator with an IC₅₀ of 61 nM.

JNJ-40068782 is a potent positive allosteric modulator of the mGlu2 receptor, with the IC₅₀ of 38 nM.

VU6010608 is a blood-brain barrier-crossing mGlu7 negative allosteric modulator (IC₅₀ = 0.76 μM). VU6010608 can block long-term enhancement (LTP) of SC-CA1 synapses in mouse brain slices induced by high-frequency stimulation. VU6010608 can be used for research on neurological diseases.

mGluR5 modulator 1 is a mGluR5 positive allosteric modulator. mGluR5 modulator 1 can be used for the research of the schizophrenia and cognitive impairments.

LY487379 hydrochloride is a selective human mGluR2 positive allosteric modulator (PAM). LY487379 hydrochloride potentiates glutamate-stimulated [³⁵S]GTPγS binding with EC₅₀ values of 1.7 μM and >10 μM for mGlu2 and mGlu3 receptors respectively. LY487379 hydrochloride promotes cognitive flexibility and facilitates behavioral inhibition in a rat model. LY487379 hydrochloride can be used for schizophrenia research.

RO5488608 is a negative allosteric metabotropic modulator of glutamate receptor 2/3. RO5488608 inhibits LY354740 (HY-18941)-induced intracellular Ca²⁺ release and can be used for study of antidepressant.

Basimglurant (RG7090; RO4917523) sulfate is a selective, orally active, blood-brain barrier permeable negative allosteric modulator of metabotropic glutamate receptor 5 (mGluR5), with a K_i of 1.4 nM (against [³H]-ABP688 (HY-110141)) and 35.6 nM (against [³H]-MPEP (HY-14609A)). Basimglurant sulfate inhibits mGlu5-mediated signaling pathways and receptor constitutive activity, regulates dopamine levels in the nucleus accumbens, exerts anxiolytic, antidepressant-like, analgesic and arousal-promoting effects, and alters δ-wave power during non-rapid eye movement sleep. Basimglurant sulfate can be used in research on depression, fragile X syndrome, anxiety disorders, etc.