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Discovery of VU2957 (Valiglurax): An mGlu4 Positive Allosteric Modulator Evaluated as a Preclinical Candidate for the Treatment of Parkinson's Disease.

ABSTRACT: Herein, we report the discovery of a novel potent, selective, CNS penetrant, and orally bioavailable mGlu4 PAM, VU0652957 (VU2957, Valiglurax). VU2957 possessed attractive in vitro and in vivo pharmacological and DMPK properties across species. To advance toward the clinic, a spray-dried dispersion (SDD) formulation of VU2957 was developed to support IND-enabling toxicology studies. Based on its overall profile, VU2957 was evaluated as a preclinical development candidate for the treatment of Parkinson's disease.

SUBMITTER: Panarese JD

PROVIDER: S-EPMC6421540 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Discovery of VU2957 (Valiglurax): An mGlu4 Positive Allosteric Modulator Evaluated as a Preclinical Candidate for the Treatment of Parkinson's Disease.

Panarese Joseph D JD Engers Darren W DW Wu Yong-Jin YJ Bronson Joanne J JJ Macor John E JE Chun Aspen A Rodriguez Alice L AL Felts Andrew S AS Engers Julie L JL Loch Matthew T MT Emmitte Kyle A KA Castelhano Arlindo L AL Kates Michael J MJ Nader Michael A MA Jones Carrie K CK Blobaum Anna L AL Conn P Jeffrey PJ Niswender Colleen M CM Hopkins Corey R CR Lindsley Craig W CW

ACS medicinal chemistry letters 20181016 3

Herein, we report the discovery of a novel potent, selective, CNS penetrant, and orally bioavailable mGlu4 PAM, VU0652957 (VU2957, Valiglurax). VU2957 possessed attractive in vitro and in vivo pharmacological and DMPK properties across species. To advance toward the clinic, a spray-dried dispersion (SDD) formulation of VU2957 was developed to support IND-enabling toxicology studies. Based on its overall profile, VU2957 was evaluated as a preclinical development candidate ...[more]

PMID: 30891122

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