Discovery of VU2957 (Valiglurax): An mGlu 4 Positive Allosteric Modulator Evaluated as a Preclinical Candidate for the Treatment of Parkinson's Disease

Joseph D. Panarese, Darren W. Engers, Yong Jin Wu, Joanne J. Bronson, John E. Macor, Aspen Chun, Alice L. Rodriguez, Andrew S. Felts, Julie L. Engers, Matthew T. Loch, Kyle A. Emmitte, Arlindo L. Castelhano, Michael J. Kates, Michael A. Nader, Carrie K. Jones, Anna L. Blobaum, P. Jeffrey Conn, Colleen M. Niswender, Corey R. Hopkins, Craig W. Lindsley

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)255-260
Number of pages6
JournalACS Medicinal Chemistry Letters
Volume10
Issue number3
DOIs
StatePublished - Mar 14 2019

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Pulse amplitude modulation
Toxicology
Modulators
Parkinson Disease
Pharmacology
In Vitro Techniques

Keywords

  • Parkinson's disease
  • Positive allosteric modulator (PAM)
  • VU2957
  • metabotropic glutamate receptor 4 (mGlu )

ASJC Scopus subject areas

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry

Cite this

Discovery of VU2957 (Valiglurax) : An mGlu 4 Positive Allosteric Modulator Evaluated as a Preclinical Candidate for the Treatment of Parkinson's Disease. / Panarese, Joseph D.; Engers, Darren W.; Wu, Yong Jin; Bronson, Joanne J.; Macor, John E.; Chun, Aspen; Rodriguez, Alice L.; Felts, Andrew S.; Engers, Julie L.; Loch, Matthew T.; Emmitte, Kyle A.; Castelhano, Arlindo L.; Kates, Michael J.; Nader, Michael A.; Jones, Carrie K.; Blobaum, Anna L.; Conn, P. Jeffrey; Niswender, Colleen M.; Hopkins, Corey R.; Lindsley, Craig W.

In: ACS Medicinal Chemistry Letters, Vol. 10, No. 3, 14.03.2019, p. 255-260.

Research output: Contribution to journalArticle

Panarese, JD, Engers, DW, Wu, YJ, Bronson, JJ, Macor, JE, Chun, A, Rodriguez, AL, Felts, AS, Engers, JL, Loch, MT, Emmitte, KA, Castelhano, AL, Kates, MJ, Nader, MA, Jones, CK, Blobaum, AL, Conn, PJ, Niswender, CM, Hopkins, CR & Lindsley, CW 2019, 'Discovery of VU2957 (Valiglurax): An mGlu 4 Positive Allosteric Modulator Evaluated as a Preclinical Candidate for the Treatment of Parkinson's Disease', ACS Medicinal Chemistry Letters, vol. 10, no. 3, pp. 255-260. https://doi.org/10.1021/acsmedchemlett.8b00426
Panarese, Joseph D. ; Engers, Darren W. ; Wu, Yong Jin ; Bronson, Joanne J. ; Macor, John E. ; Chun, Aspen ; Rodriguez, Alice L. ; Felts, Andrew S. ; Engers, Julie L. ; Loch, Matthew T. ; Emmitte, Kyle A. ; Castelhano, Arlindo L. ; Kates, Michael J. ; Nader, Michael A. ; Jones, Carrie K. ; Blobaum, Anna L. ; Conn, P. Jeffrey ; Niswender, Colleen M. ; Hopkins, Corey R. ; Lindsley, Craig W. / Discovery of VU2957 (Valiglurax) : An mGlu 4 Positive Allosteric Modulator Evaluated as a Preclinical Candidate for the Treatment of Parkinson's Disease. In: ACS Medicinal Chemistry Letters. 2019 ; Vol. 10, No. 3. pp. 255-260.
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