JNJ-46778212

JNJ-46778212 (VU 0409551) is an mGlu5 positive allosteric modulator with an EC50 of 260 nM.

Signaling Pathways >> GPCR/G Protein >> mGluR

Research Areas >> Neurological Disease

EC50: 260 nM (mGlu5)[1]

In oral brain/plasma studies, JNJ-46778212 displays excellent CNS penetration[1]. JNJ-46778212 enhances NMDAR function and rescues long-term potentiation in hippocampal slices obtained from SR−/− mice. The administration of JNJ-46778212 to SR−/− mice reverses their deficits in several neuroplasticity signaling pathways and improves their contextual fear memory[2].

Mice[1] SR−/− mice receive once daily, intraperitoneal (i.p.) injections of vehicle (20% hydroxypropyl β-cyclodextran) or VU0409551 for 5 days at a volume of 10 mL/kg. For the in vivo pharmacokinetic and dose-finding experiments, WT mice (n=5–6/dose) receive vehicle or VU0409551 (10 and 30 mg/kg). For the SR−/− mice reversal studies, WT mice receive vehicle and SR−/− mice receive either vehicle or VU0409551 (30 mg/kg). All mice are killed 2 h after the last injection on day 5[1].

[1]. Conde-Ceide S, et al. Discovery of VU0409551/JNJ-46778212: An mGlu5 Positive Allosteric Modulator Clinical Candidate Targeting Schizophrenia. ACS Med Chem Lett. 2015 May 20;6(6):716-20.

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