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James C. Barrow
James C. Barrow
Pharmacology and Molecular Sciences
Lieber Institute for Brain Development
855 N. Wolfe Street
Rangos Bldg., Room 336
Baltimore MD 21205
Drug discovery for disorders of neurodevelopment
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.
Carr GV, Chen J, Yang F, Ren M, Yuan P, Tian Q, Bebensee A, Zhang GY, Du J, Glineburg P, Xun, R, Akhile, O, Pickel, J, Barrow, JC, Papaleo, F, Weinberger, DR. KCNH2-3.1 expression impairs cognition and alters neuronal function in a model of molecular pathology associated with schizophrenia. Mol. Psychiatry. 2016, 21, 1517.
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.
Scherer PC, Ding Y, Liu Z, Xu J, Mao H, Barrow JC, Wei N, Zheng N, Snyder SS, Rao F. Inositol hexakisphosphate (IP6) generated by IP5K mediates cullin-COP9 signalosome interactions and CRL function. Proc. Nat. Acad. Sci. 2016, 113, 3503.
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.
Zhu Q, Ghoshal S, Rodrigues A, Gao S, Asterian A, Kamenecka TM, Barrow JC, Chakraborty A. Adipocyte-specific deletion of Ip6k1 reduces diet-induced obesity by enhancing AMPK-mediated thermogenesis. J Clin Invest. 2016, 126, 4273-4288.
Ghoshal S, Zhu Q, Asteian A, Lin H, Xu H, Ernst G, Barrow JC, Xu B, Cameron MD, Kamenecka TM, Chakraborty A. TNP [N2-(m-Trifluorobenzyl), N6-(p-nitrobenzyl)purine] ameliorates diet induced obesity and insulin resistance via inhibition of the IP6K1 pathway. Mol Metab. 2016 5:903-17.
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.
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.
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