James C. Barrow
855 N. Wolfe Street
Rangos Bldg., Room 374
Baltimore MD 21205
The research group is a laboratory focused on medicinal chemistry, 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.
Byers S, Buchler IP, DePasquale M, Rowley HL, Kulkarni RS, Pinder L, Kolobova A, Li C, Au V, Akuma D, Zhang G, Wei H, Cheetham SC, Barrow JC, Carr GV. Novel, non-nitrocatechol catechol-O-methyltransferase inhibitors modulate dopamine neurotransmission in the frontal cortex and improve cognitive flexibility. Psychopharm. 2020, 237, 2695.
Su, Y., DePasquale, M., Liao, G., Buchler, I., Zhang, G., Byers, S., Carr, G.V., Barrow, J. and Wei, H., Membrane bound catechol-O-methytransferase is the dominant isoform for dopamine metabolism in PC12 cells and rat brain. European Journal of Pharmacology, 2021, 896, 173909
Liao G, Ye W, Heitmann T, Ernst G, DePasquale M, Xu L, Wormald M, Hu X, Ferrer M, Harmel RK, Fiedler D, Barrow J, and Wei H Identification of Small-Molecule Inhibitors of Human Inositol Hexakisphosphate Kinases by High-Throughput Screening ACS Pharmacol. Transl. Sci. 2021, 3, 780.
Barrow JC. A Medicinal Chemist’s Perspective on Transitioning from Industry to Academic Drug Discovery. Guest Editor, ACS Med. Chem. Lett. 2019; 10: 687 https://www.ncbi.nlm.nih.gov/pubmed/31097980
Ernst G, Akuma D, Au V, Buchler IP, Byers S, Carr GV, 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 MC, Van Houtvin N, Wei H, White N, Wood M, Barrow JC. Synthesis and Evaluation of Bicyclic Hydroxypyridones as Inhibitors of Catechol O-Methyltransferase. ACS Med Chem Lett. 2019, 10, 1573-1578. https://www.ncbi.nlm.nih.gov/pubmed/32038769
Zhang G, Buchler IP, DePasquale M, Wormald M, Liao G, Wei H, Barrow JC, Carr GV. Development of a PC12 Cell Based Assay for Screening Catechol-O-methyltransferase Inhibitors. ACS Chem. Neurosci. 2019, 10,4221-4226. https://www.ncbi.nlm.nih.gov/pubmed/31491076
Wormald MM, Ernst G, Wei H, Barrow JC. Synthesis and characterization of novel isoform-selective IP6K1 inhibitors. Bioorg. Med. Chem. Lett. 2019, 29, 126628. https://www.ncbi.nlm.nih.gov/pubmed/31445853
<>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 MED, Wood M, Barrow JC Optimization of 8-Hydroxyquinolines as Inhibitors of Catechol O-Methyltransferase. J. Med. Chem. 2018, 61, 9647. https://www.ncbi.nlm.nih.gov/pubmed/30272964
Bürli RW, Wei H, Ernst G, Mariga A, Hardern IM, Herlihy K, Cross AJ, Wesolowski SS, Chen H, McKay RDG, Weinberger DR, Brandon NJ, Barrow JC. Novel inhibitors of As(III) S-adenosylmethionine methyltransferase (AS3MT) identified by virtual screening. Bioorg Med Chem Lett. 2018, 28, 3231. https://www.ncbi.nlm.nih.gov/pubmed/30170942
Wormald M, Liao G, Kimos M, Barrow J, Wei H. Development of a homogenous highthroughput assay for inositol hexakisphosphate kinase 1 activity. PLoS ONE 2017, 12(11): e0188852. https://www.ncbi.nlm.nih.gov/pubmed/29186181
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. 2016, 21, 490. https://www.ncbi.nlm.nih.gov/pubmed/26582803
Calcaterra NE, Hoeppner DJ, Wei H, Jaffe AE, Maher BJ, Barrow JC. 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. 2016, 6, 19976. https://www.ncbi.nlm.nih.gov/pubmed/26879421