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James C. Barrow

James C. Barrow
Department Affiliation: Primary: Pharmacology and Molecular Sciences;
Lieber Institute for Brain Development 
Degree: Ph.D., Harvard University
Rank: Associate Professor
Telephone Number : 410-955-0894
E-mail address: jbarrow@jhmi.edu
School of Medicine Address: Room 374, John G. Rangos, Sr., Building, 855 N. Wolfe Street, Baltimore, MD  21205
 

Drug discovery for disorders of neurodevelopment.

The research group is a laboratory focused on medicinal chemistry and drug discovery, primarily addressing diseases of neurodevelopment such as schizophrenia. Biological activity and structure-based drug design are used to drive chemistry target selection, and we are developing synthetic methods to efficiently prepare those targets. These efforts are tightly coupled with in vitro and in vivo testing and analysis, in collaboration with other research groups and core facilities at Johns Hopkins University or externally. At the core, the lab is engaged in the design and synthesis of molecules for a given biological target, analysis of in vitro and in vivo results, as well as further refinement through multiple cycles of synthesis and testing. Advances in reaction methodology, reagent availability, parallel synthesis, and purification technology now allow preparation of compounds in an efficient manner so that we can quickly drive structure-activity relationship studies and identify advanced leads. These advanced leads will have good potency and selectivity for the target of interest, and will be used to test biological hypotheses both in vitro and in vivo to determine if modulating the target is indeed a viable therapeutic strategy. By executing on medicinal chemistry programs, we will drive translational science from target and pathway discovery to novel medicines for patients.
 

Representative Publications:  

  • Calcaterra, N.E., Hoeppner, D.J., Wei, H., Jaffe, A.E., Maher, B.J., Barrow, J.C. Schizophrenia-Associated hERG channel Kv11.1-3.1 Exhibits a Unique Trafficking Deficit that is Rescued through Proteasome Inhibition for High Throughput Screening. Sci Rep. 6, 19976, 2016. Pub Med Reference
  • Kimos, M., Burton, M., Urbain, D., Caudron, D., Martini, M., Famelart, M., Gillard, M., Barrow, J., Wood, M. Development of an HTRF Assay for the Detection and Characterization of Inhibitors of Catechol-O-Methyltransferase. J Biomol Screen. 21, 490-495, 2016. Pub Med Reference
  • Wormald, M., Liao, G., Kimos, M., Barrow, J., Wei, H. Development of a homogenous highthroughput assay for inositol hexakisphosphate kinase 1 activity.  PLoS ONE 12(11): e0188852, 2017. Pub Med Reference
  • Bürli, R.W., Wei, H., Ernst, G., Mariga, A., Hardern, I.M., Herlihy, K., Cross, A.J., Wesolowski, S.S., Chen, H., McKay, R.D.G., Weinberger, D.R., Brandon, N.J., Barrow, J.C. Novel inhibitors of As(III) S-adenosylmethionine methyltransferase (AS3MT) identified by virtual screening.  Bioorg Med Chem Lett. 28, 3231-3235, 2018. Pub Med Reference
  • Buchler, I., Akuma, D., Au, V., Carr, G., de León, P., DePasquale, M., Ernst, G., Huang, Y., Kimos, M., Kolobova, A., Poslusney, M., Wei, H., Swinnen, D., Montel, F., Moureau, F., Jigorel, E., Schulze, M.E.D., Wood, M., Barrow, J.C.  Optimization of 8-Hydroxyquinolines as Inhibitors of Catechol O-Methyltransferase. J. Med. Chem. 61, 9647-9665, 2018. Pub Med Reference
  • Wormald, M.M., Ernst, G., Wei, H., Barrow, J.C. Synthesis and characterization of novel isoform-selective IP6K1 inhibitors. Bioorg. Med. Chem. Lett. 29, 126628, 2019. Pub Med Reference
  • Zhang, G., Buchler, I.P., DePasquale, M., Wormald, M., Liao, G., Wei, H., Barrow, J.C., Carr, G.V. Development of a PC12 Cell Based Assay for Screening Catechol-O-methyltransferase Inhibitors. ACS Chem. Neurosci. 10,4221-4226, 2019. Pub Med Reference
  • Ernst, G., Akuma, D., Au, V., Buchler, I.P., Byers, S., Carr, G.V., Defays, S., de León, P., Demaude, T., DePasquale, M., Durieu, V., Huang, Y., Jigorel, E., Kimos, M., Kolobova, A., Montel, F., Moureau, F., Poslusney, M., Swinnen, D., Vandergeten, M.C., Van Houtvin, N., Wei, H., White, N., Wood, M., Barrow, J.C. Synthesis and Evaluation of Bicyclic Hydroxypyridones as Inhibitors of Catechol O-Methyltransferase. ACS Med Chem Lett. 10, 1573-1578, 2019. Pub Med Reference
  • Barrow, J.C. A Medicinal Chemist’s Perspective on Transitioning from Industry to Academic Drug Discovery. Guest Editor, ACS Med. Chem. Lett. 10: 687-689, 2019. Pub Med Reference

 



Other graduate programs in which Dr. Barrow participates:  None