ML-254, also known as VU0430644; is Positive Allosteric Modulators (PAMs) of mGlu5 with Competitive MPEP-Site Interaction. ML254 is highly selective for mGlu5 versus other mGlu receptors, has a clean ancillary Ricerca profile, and suitable dystrophia myotonica protein kinase (DMPK) properties for systemic dosing in rodents. Preliminary experiments at a single dose in an in vivo model of psychosis using ML254 demonstrates a robust reversal of amphetamine induced hyperlocomotion. ML254 will serve as a significant pure-PAM tool compound for the field with potential for studies within in vivo paradigms. Structure activity relationship (SAR) and characterization of ML254 are described.
