Literature DB >> 30891122

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

Joseph D Panarese1,2, Darren W Engers1,2, Yong-Jin Wu3, Joanne J Bronson3, John E Macor3, Aspen Chun1,2, Alice L Rodriguez1,2, Andrew S Felts1,2, Julie L Engers1,2, Matthew T Loch1,2, Kyle A Emmitte1,2, Arlindo L Castelhano4, Michael J Kates4, Michael A Nader5, Carrie K Jones1,2,6, Anna L Blobaum1,2, P Jeffrey Conn1,2,6, Colleen M Niswender1,2,6, Corey R Hopkins1,2, Craig W Lindsley1,2.   

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.

Entities:  

Year:  2018        PMID： 30891122      PMCID： PMC6421540          DOI： 10.1021/acsmedchemlett.8b00426

Source DB:  PubMed          Journal:  ACS Med Chem Lett        ISSN： 1948-5875            Impact factor:   4.345


  30 in total

Review 1.  Pathophysiology of L-dopa-induced dyskinesias.

Authors:  P J Bédard; P J Blanchet; D Lévesque; J J Soghomonian; R Grondin; M Morissette; M Goulet; F Calon; P Falardeau; B Gomez-Mancilla; J P Doucet; G S Robertson; T DiPaolo
Journal:  Mov Disord       Date:  1999       Impact factor: 10.338

Review 2.  Targeting the metabotropic glutamate receptor mGluR4 for the treatment of diseases of the central nervous system.

Authors:  Michael J Marino; J Fred Hess; Nigel Liverton
Journal:  Curr Top Med Chem       Date:  2005       Impact factor: 3.295

Review 3.  Recent progress in the development of mGluR4 positive allosteric modulators for the treatment of Parkinson's disease.

Authors:  Craig W Lindsley; Colleen M Niswender; Darren W Engers; Corey R Hopkins
Journal:  Curr Top Med Chem       Date:  2009       Impact factor: 3.295

4.  Distribution and synaptic localisation of the metabotropic glutamate receptor 4 (mGluR4) in the rodent CNS.

Authors:  C Corti; L Aldegheri; P Somogyi; F Ferraguti
Journal:  Neuroscience       Date:  2002       Impact factor: 3.590

5.  Pharmacological activation of mGlu4 metabotropic glutamate receptors reduces nigrostriatal degeneration in mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.

Authors:  Giuseppe Battaglia; Carla L Busceti; Gemma Molinaro; Francesca Biagioni; Anna Traficante; Ferdinando Nicoletti; Valeria Bruno
Journal:  J Neurosci       Date:  2006-07-05       Impact factor: 6.167

Review 6.  Metabotropic glutamate receptor subtypes as targets for neuroprotective drugs.

Authors:  V Bruno; G Battaglia; A Copani; M D'Onofrio; P Di Iorio; A De Blasi; D Melchiorri; P J Flor; F Nicoletti
Journal:  J Cereb Blood Flow Metab       Date:  2001-09       Impact factor: 6.200

Review 7.  mGluR4-positive allosteric modulation as potential treatment for Parkinson's disease.

Authors:  Corey R Hopkins; Craig W Lindsley; Colleen M Niswender
Journal:  Future Med Chem       Date:  2009-06       Impact factor: 3.808

Review 8.  Preventing and controlling dyskinesia in Parkinson's disease--a view of current knowledge and future opportunities.

Authors:  Peter Jenner
Journal:  Mov Disord       Date:  2008       Impact factor: 10.338

Review 9.  Functional organization of the basal ganglia: therapeutic implications for Parkinson's disease.

Authors:  Jose A Obeso; Maria Cruz Rodríguez-Oroz; Beatriz Benitez-Temino; Franscisco J Blesa; Jorge Guridi; Concepció Marin; Manuel Rodriguez
Journal:  Mov Disord       Date:  2008       Impact factor: 10.338

10.  Synthesis and evaluation of a series of heterobiarylamides that are centrally penetrant metabotropic glutamate receptor 4 (mGluR4) positive allosteric modulators (PAMs).

Authors:  Darren W Engers; Colleen M Niswender; C David Weaver; Satyawan Jadhav; Usha N Menon; Rocio Zamorano; P Jeffrey Conn; Craig W Lindsley; Corey R Hopkins
Journal:  J Med Chem       Date:  2009-07-23       Impact factor: 7.446
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  3 in total

1.  In silico binding affinity prediction for metabotropic glutamate receptors using both endpoint free energy methods and a machine learning-based scoring function.

Authors:  Jingchen Zhai; Xibing He; Yuchen Sun; Zhuoya Wan; Beihong Ji; Shuhan Liu; Song Li; Junmei Wang
Journal:  Phys Chem Chem Phys       Date:  2022-08-03       Impact factor: 3.945

2.  Discovery of VU6028418: A Highly Selective and Orally Bioavailable M4 Muscarinic Acetylcholine Receptor Antagonist.

Authors:  Matthew Spock; Trever R Carter; Katrina A Bollinger; Changho Han; Logan A Baker; Alice L Rodriguez; Li Peng; Jonathan W Dickerson; Aidong Qi; Jerri M Rook; Jordan C O'Neill; Katherine J Watson; Sichen Chang; Thomas M Bridges; Julie L Engers; Darren W Engers; Colleen M Niswender; P Jeffrey Conn; Craig W Lindsley; Aaron M Bender
Journal:  ACS Med Chem Lett       Date:  2021-08-02       Impact factor: 4.632

Review 3.  Roles of Glutamate Receptors in Parkinson's Disease.

Authors:  Zhu Zhang; Shiqing Zhang; Pengfei Fu; Zhang Zhang; Kaili Lin; Joshua Ka-Shun Ko; Ken Kin-Lam Yung
Journal:  Int J Mol Sci       Date:  2019-09-06       Impact factor: 5.923
  3 in total

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