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Characterization of 2,4-Dianilinopyrimidines Against Five P. falciparum Kinases PfARK1, PfARK3, PfNEK3, PfPK9, and PfPKB
Open accessPublished version of a preprint
Abstract
High Resolution Image Download MS PowerPoint Slide Plasmodium kinases are increasingly recognized as potential novel antiplasmodial targets for the treatment of malaria, but only a small subset of these kinases have had structure–activity relationship (SAR) campaigns reported. Herein we report the discovery of CZC-54252 ( 1 ) as an inhibitor of five P. falciparum kinases PfARK1, PfARK3, PfNEK3, PfPK9, and PfPKB. 39 analogues were evaluated against all five kinases to establish SAR at three regions of the kinase active site. Nanomolar inhibitors of each kinase were discovered. We identified common and divergent SAR trends across all five kinases, highlighting substituents in each region that improve potency and selectivity for each kinase. Potent analogues were evaluated against the P. falciparum blood stage. Eight submicromolar inhibitors were discovered, of which 37 demonstrated potent antiplasmodial activity (EC 50 = 0.16 μM). Our results provide an understanding of features needed to inhibit each individual kinase and lay groundwork for future optimization efforts toward novel antimalarials.
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Jumper, J., Evans, R., Pritzel, A., Green, T., Figurnov, M., Ronneberger, O., Tunyasuvunakool, K., Bates, R., Žídek, A., Potapenko, A., et al. (2021) · Nature · doi:10.1038/s41586-021-03819-2 · Cited by 43,764
Development of Selective Covalent Janus Kinase 3 Inhibitors
Tan, L., Akahane, K., McNally, R., Reyskens, K. M. S. E., Ficarro, S. B., Liu, S., Herter-Sprie, G. S., Koyama, S., Pattison, M. J., Labella, K., et al. (2015) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.5b00710 · Cited by 122
Research works printed but not linked: 44
- Brown J. R., 2013, Protein Phosphorylation in Parasites, 261, 10.1002/9783527675401.ch13 · DOI
- 10.4155/fmc.12.183 · DOI
- 10.1021/acsinfecdis.0c00724 · DOI
- 10.1080/14728222.2023.2185511 · DOI
- 10.1186/1471-2164-5-79 · DOI
- 10.1002/prot.20278 · DOI
- 10.1038/ncomms1558 · DOI
- 10.1126/science.aap7847 · DOI
- 10.1007/s10822-013-9700-4 · DOI
- 10.1016/j.bmc.2015.08.006 · DOI
- 10.1038/nature09107 · DOI
- 10.1371/journal.pone.0149996 · DOI
- 10.1016/j.ejmech.2016.08.055 · DOI
- 10.1016/j.bmc.2021.116348 · DOI
- 10.1021/acsinfecdis.3c00025 · DOI
- 10.1021/cb2002413 · DOI
- 10.1021/ja104491h · DOI
- 10.1111/j.1365-2958.2010.07442.x · DOI
- 10.1111/cmi.12571 · DOI
- 10.1039/C4MD00045E · DOI
- 10.1038/s42003-020-01424-z · DOI
- 10.1016/j.febslet.2006.10.003 · DOI
- 10.1016/j.bbrc.2007.07.047 · DOI
- 10.1016/j.ejmech.2022.115043 · DOI
- 10.1073/pnas.0611601104 · DOI
- 10.1016/j.chembiol.2018.11.003 · DOI
- 10.1038/s41598-021-01267-6 · DOI
- 10.1074/jbc.M312855200 · DOI
- 10.1074/jbc.M509807200 · DOI
- 10.1016/j.molbiopara.2006.01.009 · DOI
- 10.1371/journal.pone.0035855 · DOI
- 10.1074/jbc.M708465200 · DOI
- 10.1093/nar/gkab1061 · DOI · Paper page
- 10.1021/jm400378w · DOI
- 10.1021/acs.jmedchem.1c02080 · DOI
- 10.1016/j.bmcl.2007.03.078 · DOI
- 10.1021/jacs.5b07090 · DOI
- 10.1021/jm301495v · DOI
- 10.1073/pnas.0609412103 · DOI
- 10.1111/j.1747-0285.2007.00594.x · DOI
- 10.1021/acs.jmedchem.6b00389 · DOI
- 10.1021/jm500261q · DOI
- 10.1128/AAC.48.5.1803-1806.2004 · DOI
- 10.1021/jp507569e · DOI
Metadata
- Authors
- Ong, H. W., de Silva, C., Avalani, K., Kwarcinski, F., Mansfield, C. R., Chirgwin, M., Truong, A., Derbyshire, E. R., Zutshi, R., & Drewry, D. H.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- Luceome Biotechnologies (United States) (US)
- Duke University (US)
- Corresponding author
- Derbyshire, Emily R.
- Zutshi, Reena
- Drewry, David H.
- ORCID
- Venue
- ACS Medicinal Chemistry Letters
- Publisher
- American Chemical Society (ACS)
- Published
- 2023-11-27
- Volume
- 14
- Issue
- 12
- Pages
- 1774-1784
- ISSN
- 1948-5875 (ISSN-L)
- PMC
- PMC10726455
- OpenAlex
- W4389043310
- Cited by
- 6
- References
- 2
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 1
- FWCI
- 1.54
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- ACS Medicinal Chemistry Letters (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Division of Chemistry (CHE-1726291)
- Division of Graduate Education (1644868)
- National Institute of Allergy and Infectious Diseases (1R44AI150237-01)
- Structural Genomics Consortium (1097737)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Malaria Research and Control
- Physical Sciences › Chemistry › Organic Chemistry › Heterocyclic Compound Synthesis and Bioactivity
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Drug Discovery › Phytochemical compounds biological activities
- Keywords
- kinase inhibitors, antiplasmodial agents, structure-activity relationship, malaria drug targets, blood-stage parasites, kinase selectivity
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- CoChat. (2026). Citation check: Characterization of 2,4-Dianilinopyrimidines Against Five P. falciparum Kinases PfARK1, PfARK3, PfNEK3, PfPK9, and PfPKB. https://app.cochat.ai/papers/10.1021/acsmedchemlett.3c00354
- The paper
- Ong, H. W., de Silva, C., Avalani, K., Kwarcinski, F., Mansfield, C. R., Chirgwin, M., Truong, A., Derbyshire, E. R., Zutshi, R., & Drewry, D. H. (2023). Characterization of 2,4-Dianilinopyrimidines Against Five P. falciparum Kinases PfARK1, PfARK3, PfNEK3, PfPK9, and PfPKB. ACS Medicinal Chemistry Letters. https://doi.org/10.1021/acsmedchemlett.3c00354
