1. Discovery of VU2957 (Valiglurax): An mGlu4 Positive Allosteric Modulator Evaluated as a Preclinical Candidate for the Treatment of Parkinson’s Disease
- Author
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Michael J. Kates, Arlindo L. Castelhano, Carrie K. Jones, Colleen M. Niswender, Andrew S. Felts, Anna L. Blobaum, Matthew T. Loch, Kyle A. Emmitte, Aspen Chun, John E. Macor, Joanne J. Bronson, Darren W. Engers, Alice L. Rodriguez, Julie L. Engers, Joseph D. Panarese, Craig W. Lindsley, Michael A. Nader, Wu Yong Jin, P. Jeffrey Conn, and Corey R. Hopkins
- Subjects
Allosteric modulator ,Parkinson's disease ,010405 organic chemistry ,business.industry ,Organic Chemistry ,Pharmacology ,medicine.disease ,01 natural sciences ,Biochemistry ,0104 chemical sciences ,Toxicology studies ,010404 medicinal & biomolecular chemistry ,chemistry.chemical_compound ,chemistry ,In vivo ,Drug Discovery ,medicine ,business ,Penetrant (biochemical) - Abstract
[Image: see text] Herein, we report the discovery of a novel potent, selective, CNS penetrant, and orally bioavailable mGlu(4) 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.
- Published
- 2018