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Justin  Lopchuk

Justin Lopchuk, PhD

Program: Drug Discovery

Research Program: Molecular Medicine Program


  • Overview

    1) The acceleration of drug discovery through development of new methods in organic synthesis. 2) The practical and scalable synthesis of bioactive natural products as leads in medicinal chemistry. 3) The creation of new methods and reagents for the covalent targeting of proteins with small molecules.


    • Drug Discovery
    • Head and Neck-Endocrine Oncology
    • Molecular Medicine Program

    Education & Training


    • Dartmouth College, PhD - Chemistry


    • The Scripps Research Institute - Chemistry
  • Research Interest

    Our research program is grounded in synthetic organic chemistry with a specific focus on the development of new reactions, the design of new reagents, and the total synthesis of natural products with anti-cancer activity. In collaboration with other research groups at Moffitt, we will apply our chemistry to synthesize chemical probes designed to interrogate the function of key oncoproteins and immune-regulatory proteins, while ultimately seeking to develop these probes and lead compounds into novel anti-cancer drugs. Methodology. In our ongoing quest to facilitate the rapid synthesis of bioactive molecules, we aim to develop new reactions and easy-to-use reagents centered around the deliberate use of radicals and other reactive intermediates for C–C, C–N, and C–S bond formation. Each method is designed to enable the construction of small building blocks, the modification of natural products, and the late-stage functionalization of complex molecules. Toward our goal of exploring underutilized chemical space, we will focus our attention on designing reagents which allow for the simple installation of a variety of bioisosteres. Total Synthesis. For some anti-cancer natural products, total synthesis remains the best strategy for obtaining sufficient amounts of compounds for a thorough biological evaluation, let alone the prospect of clinical trials. After carefully selecting our targets, our lab will focus on developing routes which are short, scalable, and designed to deliver multigram quantities of material for biological study, as well as the ability to synthesize libraries of analogs. Drug Discovery. Moffitt’s highly collaborative environment allows us to regularly engage with numerous biologists, chemists, and clinicians in both the Department of Drug Discovery and the Chemical Biology and Molecular Medicine Program. Here we will incorporate our new methodologies in fragment-based drug discovery, the design of chemical probes, and the chemoselective modification or tagging of bioactive molecules. The newly developed reagents and methods for installation of bioisosteres will be available for collaborators and their own lead compounds.

  • Publications

    • Teng S, Shultz ZP, Shan C, Wojtas L, Lopchuk JM. Asymmetric synthesis of sulfoximines, sulfonimidoyl fluorides and sulfonimidamides enabled by an enantiopure bifunctional S(VI) reagent. Nat Chem. 2024 Feb.16(2):183-192. Pubmedid: 38238465.
    • Karim RM, Yang L, Chen L, Bikowitz MJ, Lu J, Grassie D, Shultz ZP, Lopchuk JM, Chen J, Schönbrunn E. Discovery of Dual TAF1-ATR Inhibitors and Ligand-Induced Structural Changes of the TAF1 Tandem Bromodomain. J Med Chem. 2022 Mar.65(5):4182-4200. Pubmedid: 35191694.
    • Shultz ZP, Scattolin T, Wojtas L, Lopchuk JM. Stereospecific α-(hetero)arylation of sulfoximines and sulfonimidamides. Nat Synth. 2022 Feb.1(2):170-179. Pubmedid: 35415722. Pmcid: PMC8994872.
    • Maharaj V, Chandrachud PP, Che W, Wojtas L, Lopchuk JM. Photodecarboxylative Amination of Redox-Active Esters with Diazirines. Org Lett. 2021 Nov.23(22):8838-8842. Pubmedid: 34747619.
    • Chandrachud PP, Wojtas L, Lopchuk JM. Decarboxylative Amination: Diazirines as Single and Double Electrophilic Nitrogen Transfer Reagents. J Am Chem Soc. 2020 Dec.142(52):21743-21750. Pubmedid: 33332115.
    • Lopchuk JM, Fjelbye K, Kawamata Y, Malins LR, Pan CM, Gianatassio R, Wang J, Prieto L, Bradow J, Brandt TA, Collins MR, Elleraas J, Ewanicki J, Farrell W, Fadeyi OO, Gallego GM, Mousseau JJ, Oliver R, Sach NW, Smith JK, Spangler JE, Zhu H, Zhu J, Baran PS. Strain-Release Heteroatom Functionalization: Development, Scope, and Stereospecificity. J Am Chem Soc. 2017 Mar.139(8):3209-3226. Pubmedid: 28140573. Pmcid: PMC5334783.
    • Gianatassio R, Lopchuk JM, Wang J, Pan CM, Malins LR, Prieto L, Brandt TA, Collins MR, Gallego GM, Sach NW, Spangler JE, Zhu H, Zhu J, Baran PS. Organic chemistry. Strain-release amination. Science. 2016 Jan.351(6270):241-246. Pubmedid: 26816372. Pmcid: PMC4730898.
    • Cherney EC, Lopchuk JM, Green JC, Baran PS. A unified approach to ent-atisane diterpenes and related alkaloids: synthesis of (-)-methyl atisenoate, (-)-isoatisine, and the hetidine skeleton. J Am Chem Soc. 2014 Sep.136(36):12592-12595. Pubmedid: 25159015. Pmcid: PMC4160278.
    • Lopchuk JM, Gribble GW, Jasinski JP. Methyl 1-benzyl-5-methyl-2,4-diphenyl-1H-pyrrole-3-carboxyl-ate. Acta Crystallogr Sect E Struct Rep Online. 2014 Mar.70(Pt 3):o338-o339. Pubmedid: 24765032. Pmcid: PMC3998498.
    • Lopchuk JM, Gribble GW, Millikan SP, Jasinski JP. Bruceolline J: 2-hy-droxy-3,3-dimethyl-2,3-di-hydro-cyclo-penta-[b]indol-1(4H)-one. Acta Crystallogr Sect E Struct Rep Online. 2013.69(Pt 8):o1351-o1352. Pubmedid: 24109417. Pmcid: PMC3793830.
    • Lopchuk JM, Gribble GW, Jasinski JP. Bruceolline D: 3,3-dimethyl-1H,4H-cyclo-penta-[b]indol-2(3H)-one. Acta Crystallogr Sect E Struct Rep Online. 2013.69(Pt 7):o1043. Pubmedid: 24046619. Pmcid: PMC3772476.
    • Sporn MB, Liby KT, Yore MM, Fu L, Lopchuk JM, Gribble GW. New synthetic triterpenoids: potent agents for prevention and treatment of tissue injury caused by inflammatory and oxidative stress. J Nat Prod. 2011 Mar.74(3):537-545. Pubmedid: 21309592. Pmcid: PMC3064114.
  • Grants

    • Title: Chemical synthesis and biological evaluation of selective KRAS strain-release covalent inhibitors
      Sponsor: Moffitt Cancer Center
      PI: Lopchuk, J.
    • Title: Development of bifunctional CDK2 inhibitors for treatment of CCNE1-driven cancers
      Sponsor: Nat Institutes of Health
      PI (Contact): Schonbrunn, E., PI (MPI): Lopchuk, J.
    • Title: Selective Targeting of TAF1 Function in Acute Myeloid Leukemia
      Sponsor: Nat Institutes of Health
      PI (Contact): Schonbrunn, E., PI (MPI): Chen, J., PI (MPI): Lopchuk, J.
    • Title: Diazirines and diaziridines as nitrogen transfer reagents
      Sponsor: Nat Science Foundation
      PI: Lopchuk, J.
    • Title: New Reagents for C-C and C-N Bond Formation
      Sponsor: Nat Institutes of Health
      PI: Lopchuk, J.

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