mGluR5 Inhibitor

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.

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.

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.

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.

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).

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

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].

VU0652835 is a metabotropic glutamate receptor subtype 5 (mGlu5) negative allosteric modulator with an IC₅₀ of 81 nM.

JF-NP-26, an inactive photocaged derivative of raseglurant, is the first caged mGlu5 receptor negative allosteric modulator. Uncaging of JF-NP-26 is elicited with light pulses in the visible spectrum (405 nm). JF-NP-26 induces light-dependent analgesia in models of inflammatory and neuropathic pain in freely behaving animals.

DMeOB (3,3'-Dimethoxybenzaldazine) is a mGluR5 receptor negative allosteric modulator with an IC₅₀ of 3 μM. DMeOB displays reversible non-competitive inhibition of mGlu5-mediated responses.

PF-06422913 is an orally active, potent and selective metabotropic glutamate receptor 5 (mGluR5) negative allosteric modulator.