mGluR Modulator

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.

O-Phospho-L-serine is the immediate precursor to L-cystein 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.

VU0422288 (ML396) is a positive allosteric modulator of group III mGluRs. VU0422288 inhibits mGluRs with EC₅₀s of 125 nM, 146 nM, and 108 nM for mGluR4, mGluR7, and mGluR8, respectively in calcium mobilization assays. VU0422288 reverses deficits in contextual fear memory, social recognition, and apneas in Rett syndrome (RTT) model mice.

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).

VU6010572 is a potent, selective and brain-penetrant mGlu3 negative allosteric modulator with IC₅₀ of 245 nM. VU6010572 is highly CNS penetrant.

VU0483605 is a potent and brain-penetrated mGlu₁ receptor positive allosteric modulator (PAM). VU0483605 shows excellent mGlu₁ PAM activity at both human and rat, with EC₅₀ values of 390 and 356 nM, respectively.

CDPPB is a selective, orally active and brain-penetrant mGluR5 allosteric modulator. CDPPB increases AKT and ERK1/2 activation and augments the BDNF mRNA. CDPPB inhibits caspase-3 activation and mitochondrial dysfunction. CDPPB improves cognitive impairment, depression, and Huntington's disease.

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.

CPPHA is potent and selective positive allosteric modulator (PAM) of the mGluR5 and mGluR1 (metabotropic glutamate receptor). CPPHA can potentiate responses of mGluR5 and mGluR1 to activation of these receptors. CPPHA is developed for the research of central nervous system disorders.

Decoglurant (RO4995819) is a negative allosteric modulator of mGluR2 and mGluR3. Decoglurant is developed as an antidepressant.

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.

mGluR2 modulator 1 (compound 95) is a potent and BBB-penetrated mGluR2 (metabotropic glutamate receptor-2) positive allosteric modulator, with an EC₅₀ of 0.03 μM. mGluR2 modulator 1 can be used for psychosis research.

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

ML337 is a selective and brain-penetrant negative allosteric modulator of mGlu3, with an IC₅₀ of 593 nM. ML337 possesses a favorable dystrophia myotonica protein kinase (DMPK) and ancillary pharmacology profile. ML337 is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.

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.

VU 0364439 is a mGlu4 positive allosteric modulator with an EC₅₀ of 19.8 nM. VU 0364439 modulates the GRM4/CBX4/HIF-1α signaling pathway by enhancing GRM4-CBX4 interaction. VU 0364439 can be used for the research of parkinson’s disease.

VU6012962 is an orally bioavailable and CNS-penetrant metabotropic glutamate receptor 7 negative allosteric modulator (mGlu₇ NAM) with an IC₅₀ of 347 nM.

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

LY2389575 hydrochloride is a selective and noncompetitive mGlu3 negative allosteric modulator (NAM), with an IC₅₀ value of 190 nM. LY2389575 hydrochloride induces an increase in Mrc1 levels. LY2389575 hydrochloride also independently amplifies Amyloid beta (Aβ) toxicity and can be used in study of Alzheimer's disease.

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.