M
Matthew J. Fell
Researcher at Merck & Co.
Publications - 32
Citations - 2272
Matthew J. Fell is an academic researcher from Merck & Co.. The author has contributed to research in topics: LRRK2 & Atypical antipsychotic. The author has an hindex of 19, co-authored 27 publications receiving 1831 citations. Previous affiliations of Matthew J. Fell include University of Bradford & Eli Lilly and Company.
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Journal ArticleDOI
Phosphoproteomics reveals that Parkinson's disease kinase LRRK2 regulates a subset of Rab GTPases
Martin Steger,Francesca Tonelli,Genta Ito,Paul Davies,Matthias Trost,Melanie Vetter,Stefanie Wachter,Esben Lorentzen,Graham Duddy,Stephen S. Wilson,Marco A. S. Baptista,Brian K. Fiske,Matthew J. Fell,John A. Morrow,Alastair D. Reith,Dario R. Alessi,Matthias Mann +16 more
TL;DR: This work employs a combination of phosphoproteomics, genetics, and pharmacology to unambiguously identify a subset of Rab GTPases as key LRRK2 substrates and a novel regulatory mechanism of Rabs that connects them to PD.
Journal ArticleDOI
MLi-2, a Potent, Selective, and Centrally Active Compound for Exploring the Therapeutic Potential and Safety of LRRK2 Kinase Inhibition.
Matthew J. Fell,Christian Mirescu,Kallol Basu,Boonlert Cheewatrakoolpong,Duane E. DeMong,J. Michael Ellis,Lynn A. Hyde,Yinghui Lin,Carrie G. Markgraf,Hong Mei,Michael W. Miller,Frederique M. Poulet,Jack D. Scott,Michelle D. Smith,Zhizhang Yin,Xiaoping Zhou,Eric M. Parker,Matthew E. Kennedy,John A. Morrow +18 more
TL;DR: The suitability of MLi-2 as a compound to explore LRRK2 biology in cellular and animal models is demonstrated, with greater than 295-fold selectivity for over 300 kinases in addition to a diverse panel of receptors and ion channels.
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Evidence for the Role of Metabotropic Glutamate (mGlu)2 Not mGlu3 Receptors in the Preclinical Antipsychotic Pharmacology of the mGlu2/3 Receptor Agonist (–)-(1R,4S,5S,6S)-4-Amino-2-sulfonylbicyclo[3.1.0]hexane-4,6-dicarboxylic Acid (LY404039)
TL;DR: The data demonstrate that the antipsychotic-like effects of the mGlu2/3 receptor agonist LY404039 in psychostimulant models of psychosis are mechanistically distinct from those of atypical antipsychotics drugs and are dependent on functional mGLU2 and notmGlu3 receptors.
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N-(4-((2-(trifluoromethyl)-3-hydroxy-4-(isobutyryl)phenoxy)methyl)benzyl)-1-methyl-1H-imidazole-4-carboxamide (THIIC), a Novel Metabotropic Glutamate 2 Potentiator with Potential Anxiolytic/Antidepressant Properties: In Vivo Profiling Suggests a Link between Behavioral and Central Nervous System Neurochemical Changes
Matthew J. Fell,Jeffrey M. Witkin,Julie F. Falcone,Jason Katner,Kenneth W. Perry,John Hart,Linda M. Rorick-Kehn,Carl D Overshiner,Kurt Rasmussen,Stephen F. Chaney,Mark J. Benvenga,Xia Li,Deanna L Marlow,Linda K. Thompson,Susan K Luecke,Keith A. Wafford,Wesley F. Seidel,Dale M. Edgar,Anne T. Quets,Christian C. Felder,Xushan Wang,Beverly A. Heinz,Alexander Nikolayev,Ming-Shang Kuo,Daniel Ray Mayhugh,Albert Khilevich,Deyi Zhang,Phillip J Ebert,James E Eckstein,Bradley L. Ackermann,Steven P. Swanson,John T. Catlow,Robert A. Dean,Kimberley Jackson,Sitra Tauscher-Wisniewski,Gerard J. Marek,Jeffrey M. Schkeryantz,Kjell Svensson +37 more
TL;DR: The results indicate that the novel mGlu2-positive allosteric modulator THIIC has robust activity in models used to predict anxiolytic/antidepressant efficacy, substantiating, at least with this molecule, differentiation in the biological impact of mGLU2 potentiation versus mGlam2/3 orthosteric agonism.
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Discovery of a 3-(4-Pyrimidinyl) Indazole (MLi-2), an Orally Available and Selective Leucine-Rich Repeat Kinase 2 (LRRK2) Inhibitor that Reduces Brain Kinase Activity.
Jack D. Scott,Duane E. DeMong,Thomas J. Greshock,Kallol Basu,Xing Dai,Joel M. Harris,Alan Hruza,Sarah W. Li,Sue-Ing Lin,Hong Liu,Megan K. Macala,Zhiyong Hu,Hong Mei,Honglu Zhang,Paul L. Walsh,Marc Poirier,Zhi-Cai Shi,Li Xiao,Gautam Agnihotri,Marco A. S. Baptista,John Columbus,Matthew J. Fell,Lynn A. Hyde,Reshma Kuvelkar,Yinghui Lin,Christian Mirescu,John A. Morrow,Zhizhang Yin,Xiaoping Zhang,Xiaoping Zhou,Ronald K. Chang,Mark W. Embrey,John M. Sanders,Heather E. Tiscia,Robert E. Drolet,Jonathan T. Kern,Sylvie M. Sur,John J. Renger,Mark T. Bilodeau,Matthew E. Kennedy,Eric M. Parker,Andrew Stamford,Ravi P. Nargund,John A. Mccauley,Michael W. Miller +44 more
TL;DR: Genetic validation for inhibition of LRRK2 kinase activity as a potential means of affecting disease progression, and the development of MLi-2: a potent, highly selective, orally available, brain-penetrant inhibitor of L RRK2.