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Discovery of a potent, selective and orally active in vivo mGlu4 positive allosteric modulator.


Probe Reports from the NIH Molecular Libraries Program [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2010-.
2010 Oct 29 [updated 2013 Mar 14].


ML182 was identified through a medicinal chemistry campaign that was designed to improve the in vivo characteristics of ML128. ML182 is a potent and novel positive allosteric modulator (PAM) of the metabotropic glutamate receptor 4 (mGlu4) – hEC50 = 291 nM; rEC50 = 376 nM. ML182 shows excellent in vitro and in vivo pharmacokinetic characteristics and was shown to be active in an anti-Parkinsonian animal model after oral dosing (haloperidol-induced catalepsy). This will find utility in the Parkinson’s and mGlu community as a novel, selective and potent PAM of mGlu4.

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