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

doi:10.1021/acsmedchemlett.8b00426

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 journal › Article › peer-review

22 Scopus citations

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 language	English (US)
Pages (from-to)	255-260
Number of pages	6
Journal	ACS Medicinal Chemistry Letters
Volume	10
Issue number	3
DOIs	https://doi.org/10.1021/acsmedchemlett.8b00426
State	Published - Mar 14 2019
Externally published	Yes

Keywords

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

ASJC Scopus subject areas

Biochemistry
Drug Discovery
Organic Chemistry

Access to Document

10.1021/acsmedchemlett.8b00426

Cite this

Panarese, J. D., Engers, D. W., Wu, Y. J., Bronson, J. J., Macor, J. E., Chun, A., Rodriguez, A. L., Felts, A. S., Engers, J. L., Loch, M. T., Emmitte, K. A., Castelhano, A. L., Kates, M. J., Nader, M. A., Jones, C. K., Blobaum, A. L., Conn, P. J., Niswender, C. M., Hopkins, C. R., & Lindsley, C. W. (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, 10(3), 255-260. https://doi.org/10.1021/acsmedchemlett.8b00426

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

Research output: Contribution to journal › Article › peer-review

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

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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.",

keywords = "Parkinson's disease, Positive allosteric modulator (PAM), VU2957, metabotropic glutamate receptor 4 (mGlu )",

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

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