mGluR Inhibitor

VU6066098 is a blood-brain barrier penetrant, orally active inhibitor of metabotropic glutamate receptor subtype 2 (mGlu2), with IC₅₀ values of 77 nM and 111 nM against human and rat targets, respectively. VU6066098 induces antidepressant-like activity, inhibits psychosis-like hyperlocomotion, enhances recognition memory and associative learning, and reverses cognitive deficits caused by blast-related traumatic brain injury. VU6066098 can be used in research on major depressive disorder, schizophrenia, Alzheimer's disease, and traumatic brain injury.

Basimglurant (RG7090; RO4917523) 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 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 can be used in research on depression, fragile X syndrome, anxiety disorders, etc.

CALP1 TFA is a calmodulin (CaM) agonist (K_d of 88 µM) with binding to the CaM EF-hand/Ca²⁺-binding site. CALP1 TFA blocks calcium influx and apoptosis (IC₅₀ of 44.78 µM) through inhibition of calcium channel opening. CALP1 TFA blocks glutamate receptor channels and blocks a store-operated nonselective cation channel. CALP1 TFA activates CaM-dependent phosphodiesterase activity.

VU6001966 is a brain-penetrant and selective mGlu2 receptor inhibitor. VU6001966 blocks mGlu2 receptor activity, counteracts LY379268 (HY-103558)-mediated blood-brain barrier protection and inflammatory cytokine dampening in microglia under inflammatory conditions. VU6001966 enhances antidepressant effects when combined with Scopolamine (HY-N0296). VU6001966 can be used for the research of major depressive disorder.

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

HTL14242 (HTL0014242) is an advanced and orally active mGlu5 NAM with a pK_i and a pIC₅₀ of 9.3 and 9.2, respectively. HTL14242 can be used for the research of parkinson’s disease.

FITM is a negative allosteric modulator of mGlu1 receptor with a K_i of 2.5 nM.

JNJ-46281222 is an metabotropic glutamate (mGlu) 2-selective, highly potent PAM (positive allosteric modulator) with nanomolar affinity (K_d = 1.7 nM) and a high modulatory potency (pEC₅₀ = 7.71).

FTIDC is an orally active, noncompetitive, selective allosteric metabotropic glutamate receptor (mGluR) 1 antagonist with an IC₅₀ of 5.8 nM for human mGluR1a. FTIDC has no species differences in its antagonistic activity on recombinant human, mouse, and rat mGluR1.

ML289 (VU0463597) is a potent, selective, and CNS-penetrant mGlu3 (IC₅₀=0.66 μM) negative allosteric modulator. ML289 displays >15-fold selectivity over mGlu2 and is inactive against mGlu5. ML289 is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.

VU6043653 is a potent, selective and cross the blood-brain barrier metabotropic glutamate receptor subtype 5 (mGlu5) negative allosteric modulator with an IC₅₀ value of 325 nM for h mGlu5.

AZD6538 is a potent, selective and brain penetrant mGluR5 negative allosteric modulator. AZD6538 inhibits DHPG (HY-12598A)-stimulated intracellular Ca2+ release in HEK cells expressing rat or human mGluR5, with IC₅₀ values of 3.2 and 13.4 nM for rat mGluR5 and human mGluR5, respectively. AZD6538 can be used for the research of neuropathic pain.

Naftazone is a naphthoquinone derivative, it can be used for the research of venous insufciency. Naftazone protects blood vessels, increases venous tonicity and capillary resistance, and improves lymphatic and venous circulation.

Auglurant (VU0424238) is a novel and selective mGlu5 antagonist with an IC₅₀ value of 11 nM (rat) and an IC₅₀ value of 14 nM (human). Auglurant (VU0424238) has an acceptable CNS penetration.

VU0409106 is a potent and selective mGlu₅ negative allosteric modulator (NAM) with an IC₅₀ of 24 nM. VU0409106 shows anxiolytic effects in rat models in a concentration-dependent manner. VU0409106 also penetrates the blood-brain barrier (BBB).

CALP1 is a calmodulin (CaM) agonist (K_d of 88 µM) with binding to the CaM EF-hand/Ca²⁺-binding site. CALP1 blocks calcium influx and apoptosis (IC₅₀ of 44.78 µM) through inhibition of calcium channel opening. CALP1 blocks glutamate receptor channels and blocks a store-operated nonselective cation channel. CALP1 activates CaM-dependent phosphodiesterase activity.

BMT-145027 is an mGluR5 positive allosteric modulator without inherent agonist activity, exhibits an EC₅₀ of 47 nM.

N. N-dipropyrldopamine is a potent inhibitor of glutamate release and has anticancer activity. The increase of glutamate secretion leads to cancer-induced bone pain (CIBP). N. N-dipropyrldopamine plays an analgesic role in CIBP.

AZD 9272 is a selective, orally active and brain penetrant mGluR5 antagonist with IC₅₀s of 2.6 nM and 7.6 nM for rat and human receptors, respectively. AZD 9272 shows >3900-fold selectivity over other mGlu receptors^2].

DFMTI can completely block the rmGlu1 L757V glutamate response.