mGluR3 Modulator

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.

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

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

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.

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.