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

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

  • ACS Med Chem Lett. 2018 Oct 16;10(3):255-260. doi: 10.1021/acsmedchemlett.8b00426.
Joseph D Panarese 1 2,  Darren W Engers 1 2,  Yong-Jin Wu 3,  Joanne J Bronson 3,  John E Macor 3,  Aspen Chun 1 2,  Alice L Rodriguez 1 2,  Andrew S Felts 1 2,  Julie L Engers 1 2,  Matthew T Loch 1 2,  Kyle A Emmitte 1 2,  Arlindo L Castelhano 4,  Michael J Kates 4,  Michael A Nader 5,  Carrie K Jones 1 2 6,  Anna L Blobaum 1 2,  P Jeffrey Conn 1 2 6,  Colleen M Niswender 1 2 6,  Corey R Hopkins 1 2,  Craig W Lindsley 1 2
Affiliations

Affiliations

  • 1 Department of Pharmacology, Vanderbilt University, Nashville, Tennessee 37232, United States.
  • 2 Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, Tennessee 37232, United States.
  • 3 Bristol-Myers Squibb Co., Research & Development, 5 Research Parkway, Wallingford, Connecticut 06492 United States.
  • 4 Davos Pharma, A Davos Chemical Company, 600 East Crescent Ave., Upper Saddle River, New Jersey 07458, United States.
  • 5 Center for the Neurobiology of Addiction Treatment, Wake Forest School of Medicine, Medical Center Boulevard Winston-Salem, North Carolina 27157, United States.
  • 6 Vanderbilt Kennedy Center, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, United States.
PMID: 30891122 DOI: 10.1021/acsmedchemlett.8b00426
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.

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