Basimglurant

Basimglurant (RG7090) is a potent, selective and orally available mGlu5 negative allosteric modulator with a Kd of 1.1 nM.

Signaling Pathways >> GPCR/G Protein >> mGluR

Research Areas >> Neurological Disease

Kd: 1.1 nM (mGlu5)[1]

[3H]-basimglurant saturation analysis on recombinant human mGlu5 reveals monophasic saturation isotherms with Kd of 1.1 nM. In competition binding experiments on human recombinant mGlu5, Basimglurant (RG7090) fully displaces [3H]-MPEP with a Ki of 35.6 nM and [3H]-ABP688 with a Ki of 1.4 nM. In HEK293 cells stably expressing human mGlu5, Basimglurant (RG7090) inhibits quisqualate induced Ca2+ mobilization with an IC50 of 7.0 nM and [3H]-inositolphosphate accumulation with an IC50 of 5.9 nM. Basimglurant (RG7090) shows similar potencies in radioligand binding and functional assay on human and rodent mGlu5 receptor orthologues[1].

Basimglurant (RG7090) is a potent, selective, and safe mGlu5 inhibitor with good oral bioavailability and long half-life supportive of once-daily administration, good brain penetration, and high in vivo potency. It has antidepressant properties which are corroborated by its functional magnetic imaging (fMRI) profile, as well as anxiolytic-like and antinociceptive features[1]. It is currently in phase II clinical studies for the treatment of depression and fragile X syndrome. In the Vogel conflict drinking test, Basimglurant dose dependently increases the drinking time. The total plasma exposure of efficacious doses of Basimglurant (RG7090) ranges from 5 ng/mL (0.03 mg/kg) to 37 ng/mL (0.3 mg/kg)[2].

Rats: For intravenous PK, Basimglurant (RG7090) is formulated in N-methyl-pyrollidone (NMP)/saline (30%/70%) as vehicle and administered at a volume of 2 mL/kg. For oral gavage (p.o.) the compound is administered as suspension using gelatine/saline (7.5%/0.62% in water) at an administration volume of 4 mL/kg[1]. Monkey: For intravenous PK, Basimglurant (RG7090) is formulated in cyclodextrin solution as vehicle and administered at a volume of 2 mL/kg. For oral gavage (p.o.), the compound is administered in capsule (2 mg in size-2 capsules, i.e. ~0.3 mg/kg) to fasted or fed monkeys in a cross-over design[1].

[1]. Lindemann L, et al. Pharmacology of basimglurant (RO4917523, RG7090), a unique metabotropic glutamate receptor 5 negative allosteric modulator in clinical development for depression. J Pharmacol Exp Ther. 2015 Apr;353(1):213-33.

[2]. Jaeschke G, et al. Metabotropic glutamate receptor 5 negative allosteric modulators: discovery of 2-chloro-4-[1-(4-fluorophenyl)-2,5-dimethyl-1H-imidazol-4-ylethynyl]pyridine (basimglurant, RO4917523), a promising novel medicine for psychiatric diseases.

mavoglurant | L-Glutamine | CTEP (RO4956371) | LY 354740 | L-(+)Sodium glutamate | ADX-88178 | MPEP (Hydrochloride) | FITM | (S)-MCPG | LY341495 | Dipraglurant | JNJ-40411813 | LY404039 | JNJ 16259685 | ADX-47273