mGluR Modulator

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.

VU6081679 is an orally active positive allosteric modulator of mGlu8 with blood-brain barrier permeability. VU6081679 binds to the extracellular allosteric pocket at the TM6/TM7 junction of mGlu8, and anchors via hydrophobic interactions and water-mediated polar contacts, thereby stabilizing the active state of the receptor and exerting positive allosteric regulatory effects. VU6081679 can be used for research on Parkinson's disease.

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.

AZD-8418 is an orally active positive allosteric modulator of metabotropic glutamate receptor 2 (mGluR2), with an EC₅₀ of 0.86 μM for rat mGlu2 receptors. AZD-8418 reduces the in vitro binding level of [³H]AZ12559322 in prefrontal cortex brain tissues of non-human primates. AZD8418 enhances the inhibitory effect of the mGlu2/3 agonist DCG-IV (HY-101335) on field excitatory postsynaptic potentials (fEPSP) in rat hippocampal brain slices. AZD-8418 reduces nicotine self-administration behavior in rats, and blocks cue-induced reinstatement of nicotine-seeking and food-seeking behaviors. The attenuating effect on nicotine self-administration behavior develops rapid tolerance, while inhibition of food self-administration behavior requires chronic administration. AZD-8418 can be used in research related to nicotine dependence and neuropsychiatric disorders.

mGluR2 modulator 2 (compound 2) is a potent, selective and orally bioavailable mGluR2 positive allosteric modulator with an EC₅₀ value of 0.13 μM. mGluR2 modulator 2 can be used for researching antipsychotic.

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.

mGlu4 receptor agonist 1 (compound 62) is a potent mGlu4 receptor positive allosteric modulator, with an EC₅₀ of 308 nM. mGlu4 receptor agonist 1 shows significant anxiolytic- and antipsychotic-like effect.

VU6031545 is a potent mGlu 5 negative allosteric modulator with an IC₅₀ of 15 nM. VU6031545 has excellent brain penetrant and oral bioavailability in rats.

VU0404251 is a highly potent positive allosteric modulator of mGlu for the study of psychosis.

(S)-4C3HPG ((S)-4-Carboxy-3-hydroxyphenylglycine) is an antagonist of mGluR1a and an agonist of mGluR2. (S)-4C3HPG has the anticonvulsant activity and protects against audiogenic seizures in DBA/2 mice.

VU6053371 (BI03738809) is a first-in-class (FIC), selective, orally active, and brain-penetrant metabotropic glutamate receptor subtype 3 (mGlu3) positive allosteric modulator (PAM) with EC₅₀s of 103 nM and 112 nM for human and rat mGlu3. VU6053371 exhibits selectivity for mGlu3 over other mGlu receptor subtypes. VU6053371 exhibits pro-cognitive effects in mouse models. VU6053371 can be used in research schizophrenia, Alzheimer’ s disease and other forms of dementia and cognitive impairment.

AZ12559322 is a positive allosteric modulator of mGluR2, with the K_i value of 1.31 nM. AZ12559322 can be used in neurological research.

VU0240382 is a metabotropic glutamate receptor subtype 5 modulator whose activity differs depending on whether it has allosteric agonist activity. VU0240382 with allosteric agonist activity can activate mGlu(5) receptors in cell lines, but has no agonist activity in natural systems and has similar efficacy to mGlu(5) modulators without allosteric agonist activity in animal models.

VU0418506 is a selective positive allosteric modulator of mGlu₄, with EC₅₀ values of 68 nM and 46 nM for hmGlu₄ and rmGlu₄, respectively. VU0418506 exhibits antiparkinsonian activity.

VU0410425 is an mGlu₁ negative allosteric modulator. VU0410425 exhibits potent inhibitory activity for rat mGlu₁ with an IC₅₀ value of 140 nM. VU0410425 can be used for the research of central nervous system disorders.

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

mGluR2 modulator 6 (Compound 25-a) is a mGluR2 modulator. mGluR2 modulator 6 has anticonvulsant activity in the 6Hz epilepsy model, and the effect is better when combined with Levetiracetam (HY-B0106). mGluR2 modulator 6 can be used in the research of epilepsy.

VU0469650 hydrochloride is a brain-penetrant negative allosteric modulator of metabotropic glutamate receptor 1 (mGluR1). VU0469650 hydrochloride inhibits glutamate-induced calcium flux in cells expressing human mGluR1 (IC₅₀= 99 nM). VU0469650 hydrochloride is promising for research of central nervous system diseases such as anxiety, addiction, and epilepsy.