47464-Monn, James
Faculty

James A. Monn, PHD

Adjunct Clinical Professor of Medicine

Bio

James Monn, PhD, obtained his bachelor of science degree in Chemistry from St. John’s University (MN), his doctorate degree in Medicinal Chemistry at the University of Kansas and his postdoctoral training at the National Institutes of Health. He took a position as a Senior Organic Chemist at Eli Lilly and Company in 1989, focusing on the discovery of novel agents for the treatment of CNS disorders and has continued to work on CNS-associated targets since that time. Following 28 years of service, Dr. Monn retired from Lilly in December of 2017. Since then, he has worked as an Independent Scientific Consultant, Head of Chemistry at Anagin, Inc. (Indianapolis, IN) and Vice President of Chemistry at Karuna Therapeutics, Inc. (Boston, MA).  While at Lilly, Dr. Monn was regarded as an accomplished scientific team leader, guiding several multidisciplinary teams toward the delivery of clinical candidates. He is internationally recognized as a pioneer in the discovery of novel therapeutic agents targeting metabotropic glutamate receptors including Eglumegad and Talaglumetad-HCl (Anxiety Disorders), Pomaglumetad Methionil (Schizophrenia) and LY2979165 (Psychosis and Agitation in Dementia). He also held roles as a scientific group leader, advisor to numerous drug discovery teams, peer mentor and was a member of various discovery research oversight groups. While the majority of his research has centered on glutamatergic mechanisms for the treatment of psychiatric and neurologic disorders, Dr. Monn has had leadership responsibilities for discovery teams focused on other target classes including voltage gated ion channels, enzymes, and protein-protein interactions. He has authored or co-authored over 100 peer-reviewed publications, 18 reviews and book chapters, 200 abstracts, is recognized as an inventor on 40 patents and holds professional memberships with the American Chemical Society, ACS Division of Medicinal Chemistry and the Society for Neuroscience.

Key Publications

Monn, J. A., Valli, M. J., Massey, S. M., Wright, R. A., Salhoff, C. R., Johnson, B. G., Howe, T., Alt, C. A., Rhodes, G. A., Robey, R. L., Griffey, K. R., Tizzano, J. P., Kallman, M. J., Helton, D. R. and Schoepp, D. D. “Design, synthesis and pharmacological characterization of (+)-2-aminobicyclo[3.1.0]hexane-2,6-dicarboxylic Acid (LY354740): a potent, selective and orally active group 2 metabotropic glutamate receptor agonist possessing anticonvulsant and anxiolytic properties” J. Med. Chem. 1997, 40, 528-537.

Helton, D. R., Tizzano, J. P., Monn, J. A., Schoepp, D. D. and Kallman, M. J. “Anxiolytic and side-effect profile of LY354740: a potent, highly selective, orally active agonist for group II metabotropic glutamate receptors” J. Pharmacol. Exp. Ther., 1998, 284, 651-660.

McKinzie, D. L., Monn, J. A., Levine, L R., Schoepp, D. D., Martenyi, F., Tauscher-Wisniewski, S., Dellva, M. A., Potter, W. Z., Gaydos, B. L., Conley, R. “Efficacy and Safety of the Metabotropic Glutamate 2/3 Receptor Agonist LY354740 Versus Lorazepam in a Double-Blind, Placebo-Controlled Study of Patients with a Primary Diagnosis of Generalized Anxiety Disorder” J. Clin. Psychopharmacol., 2018, under review.

Monn, J. A., Valli, M. J., Massey, S. M., Henry, S. S., Stephenson, G. A., Bures, M., Herin, M., Catlow, J., Giera, D., Wright, R. A., Johnson, B. G., Andis, S. L., Kingston, A. E., Schoepp, D. D. “Synthesis and metabotropic glutamate receptor activity of S-oxidized variants of LY389795: Identification of potent, selective and orally bioavailable agonists for mGlu2/3 receptors” J. Med. Chem, 2007, 50, 233-240.

Rorick-Kehn, L. M., Johnson, B. G., Knitowski, K. M., Salhoff, C. R., Witkin, J. M., Perry, K. W., Griffey, K. I., Monn, J. A., McKinzie, D. L., Schoepp, D. D. “Pharmacological properties of a structurally-novel, potent, selective mGlu2/3 receptor agonist: In vivo characterization of LY404039 in animal models of psychiatric disorders” Psychopharmacology, 2007, 193, 121-136.

Patil, S. T., Zhang, L. X., Martenyi, F., Lowe, S. L., Jackson, K. A., Andreev, B. V., Alla S. Avedisova, A. S., Bardenstein, L. M., Gurovich, I. Y., Morozova, M. A. Mosolov, S. N., Neznanov, N. G., Reznik, A. M., Smulevich, A. B., Tochilov, V. A., Johnson, B. G., Monn, J. A., Schoepp, D. D. “Activation of mGlu2/3 receptors as a new approach to treat schizophrenia: results from a Phase 2 clinical trial” Nature Medicine, 2007, 13, 1102-1107.

Monn, J. A., Prieto, L., Taboada, L., Hao, J., Reinhard, M. R., Henry, S. S., Beadle, C., Walton, L., Man, T., Rudyk, H., Clark, B., Tupper, D., Baker, S. R., Lamas, C., Montero, C., Marcos, A., Blanco, J., Bures, M. G., Clawson, D. K., Atwell, S., Lu, F., Wang, J., Russell, M., Heinz, B. A., Wang, X., Carter, J., Getman, B., Catlow, J., Swanson, S., Johnson, B. G., Shaw, D., McKinzie, D. L. “Synthesis and pharmacological characterization of C4-(thiotriazolyl)-substituted-2-aminobicyclo[3.1.0]hexane-2,6-dicarboxylates. Identification of (1R,2S,4R,5R,6R)-2-amino-4-(1H-1,2,4-triazol-3-ylsulfanyl)bicyclo[3.1.0]hexane-2,6-dicarboxylic Acid (LY2812223), a highly potent, functionally selective mGlu2 receptor agonist” J. Med. Chem., 2015, 58, 7526-7548.

Felder, C., Tu, Y., Schober, D., Quets, A., Xiao, H., Watt, M., Siuda, E., Nisenbaum, E., Xiang, C., Heinz, B., Prieto, L., McKinzie, D., Monn, J. “Translational pharmacology of the mGluR2-preferring agonist LY2812223 in animal and human brain” J. Pharmacol. Exp. Ther. 2017, 361, 190-197.

Monn, J. A., Prieto, L., Taboada, L., Hao, J., Reinhard, M. R., Henry, S. S., Beadle, C., Walton, L., Man, T., Rudyk, H., Clark, B., Tupper, D., Baker, S. R., Lamas, C., Montero, C., Marcos, A., Blanco, J., Bures, M. G., Atwell, S., Lu, F., Wang, J., Russell, M., Heinz, B.A., Wang, X., Carter, J., Getman, B., Catlow, J., Swanson, S., Johnson, B. G., Shaw, D., McKinzie, D. L. “Synthesis and pharmacological characterization of C4-disubstituted analogs for 1S,2S,5R,6S-2-aminobicyclo[3.1.0]hexane-2,6-dicarboxylate: Identification of a potent, selective metabotropic glutamate receptor agonist and determination of agonist-bound human mGlu2 and mGlu3 amino terminal domain structures” J. Med. Chem., 2015, 58, 1776-1794.

Johnson, M. P., Muhlhauser, M. A., Nisenbaum, E. S., Simmons, R. M. A., Forster, B. M., Knopp, K. L., Yang, L., Morrow, D., Li, D. L., Kennedy, J. D., Swanson, S., Monn, J. A. “Broad spectrum efficacy with LY2969822, a metabotropic glutamate 2/3 agonist prodrug of LY2934747, in rodent pre-clinical pain models. Br. J. Pharmacol., 2017, 174, 822-835.

Chappell, M. D., Li, R., Smith, S., Dressman, B. A., Tromiczak, E. G., Tripp, A. E., Blanco, M. J., Vetman, T., Quimby, S. J., Matt, J., Britton, T., Fivush, A. M., Schkeryantz, J. M., Khilevich, A., Jaramillo, C., Carpintero, M., de Diego, J. E., Barberis, M., Garcia, S., Soriano, J. F., Witkin, J. M., Xiang, C., Li, X., Overshiner, C., Wafford, K. A., Seidel, W., Wang, X.-S., Heinz, B., Swanson, S., Catlow, J, Bedwell, D., Clawson, D. K., Monn, J. A., Mitch, C. H., Ornstein, P. L., “Discovery of (1S,2R,3S,4S,5R,6R)-2-amino-3-[(3,4-difluorophenyl)sulfanylmethyl]-4-hydroxy-bicyclo[3.1.0]hexane-2,6-dicarboxylic acid hydrochloride (LY3020371) a potent, selective metabotropic glutamate receptor 2/3 co-antagonist with in vivo antidepressant activity”   J. Med. Chem., 2016, 59, 10974-10993.

Witkin, J. M., Mitchell, S. N., Wafford, K. A., Carter, G., Gilmour, G., Li, J., Eastwood, B. J.,   Overshiner, C., Li, X., Rorick-Kehn, L., Rasmussen, K., Svensson, K., Falcone, J., Nikolayev, A., VV Tolstikov, V. V., Kuo, M.-S., Li, R., Smith, S. C., Mitch, C. H., Ornstein, P. L., Swanson, S., Monn, J. A. “Comparative effects of LY3020371, a potent and selective mGlu2/3 receptor antagonist and ketamine, a non-competitive NMDA receptor antagonist in rodents. Evidence supporting the use of mGlu2/3 antagonists for the treatment of depression” J. Pharmacol. Exp. Ther, 2017, 361, 68-86.

Witkin, J. M., Monn, J. A., Li, J., Johnson, B., McKinzie, D. L., Wang, X.-S., Heinz, B. A., Li, R., Ornstein, P. L., Smith, S. C., Mitch, C. H., Calligaro, D. O., Swanson, S., Allen, D., Phillips, K., Gilmour, G. Preclinical predictors that the orthosteric mGlu2/3 receptor antagonist LY3020371 will not engender ketamine-associated neurotoxic, motor, cognitive, subjective, or abuse liability-related effects. Pharmacol. Biochem. Behav., 2017, 155, 43-55.

Monn, J. A., Henry, S. S., Hao, J., Massey, S. M., Clawson, D. K., Atwell, S., Lu, F., Wang, J., Russell, M., Heinz, B. A., Wang, X., Carter, J. H., Getman, B. G., Catlow, J. T., Swanson, S., Johnson, B. G., Shaw, D., McKinzie, D. L. “Synthesis and pharmacological characterization of C4?-amide-Substituted 2-aminobicyclo[3.1.0]hexane-2,6-dicarboxylates. Identification of (1S,2S,4S,5R,6S)-2-amino-4-[(3-methoxybenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic acid (LY2794193), a highly potent mGlu3 receptor-selective agonist. J. Med. Chem., 2018, 61, 2303-2328.

Titles & Appointments

  • Adjunct Clinical Professor of Medicine
  • Education
    1987 PHD University of Kansas
    1981 BS Saint John's University
  • Research

    Dr. Monn's current research interests include the design and synthesis of small molecules capable of modulating the signaling of NMDA, metabotropic glutmate 2/3 and muscarinic cholinergic receptors in the central nervous system and use of these as novel treatments for psychiatric and neurologic disorders.

  • Professional Organizations
    American Chemical Society
    Society for Neuroscience

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