Large-scale cytological profiling for functional analysis of bioactive compounds
Abstract
Cytological profiling (CP) is an unbiased image-based screening technique that uses automated microscopy and image analysis to profile compounds based on numerous quantifiable phenotypic features. We used CP to evaluate a library of nearly 500 compounds with documented mechanisms of action (MOAs) spanning a wide range of biological pathways. We developed informatics techniques for generating dosage-independent phenotypic “fingerprints” for each compound, and for quantifying the likelihood that a compound's CP fingerprint corresponds to its annotated MOA. We identified groups of features that distinguish classes with closely related phenotypes, such as microtubule poisons vs. HSP90 inhibitors, and DNA synthesis vs. proteasome inhibitors. We tested several cases in which cytological profiles indicated novel mechanisms, including a tyrphostin kinase inhibitor involved in mitochondrial uncoupling, novel microtubule poisons, and a nominal PPAR-gamma ligand that acts as a proteasome inhibitor, using independent biochemical assays to confirm the MOAs predicted by the CP signatures. We also applied maximal-information statistics to identify correlations between cytological features and kinase inhibitory activities by combining the CP fingerprints of 24 kinase inhibitors with published data on their specificities against a diverse panel of kinases. The resulting analysis suggests a strategy for probing the biological functions of specific kinases by compiling cytological data from inhibitors of varying specificities.
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Using multiple marker panels allows surveying a broader spectrum of features and can reduce the risk of bleed-through between fluorescent channels.
“Using multiple marker panels19,23 allows for surveying a broader spectrum of features and can reduce the risk of bleed-through between fluorescent channels depending on the assay design.”
From A statistical framework for high-content phenotypic profiling using cellular feature distributions (2022) · cites this paper as [19]
Cites
Subramanian, A., Tamayo, P., Mootha, V. K., Mukherjee, S., Ebert, B. L., Gillette, M. A., Paulovich, A., Pomeroy, S. L., Golub, T. R., Lander, E. S., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0506580102 · Cited by 53,625 · see citing works
Mootha, V. K., Lindgren, C. M., Eriksson, K.-F., Subramanian, A., Sihag, S., Lehar, J., Puigserver, P., Carlsson, E., Ridderstråle, M., Laurila, E., et al. (2003) · Nature Genetics · doi:10.1038/ng1180 · Cited by 10,197 · see citing works
Detecting Novel Associations in Large Data Sets
Reshef, D. N., Reshef, Y., Finucane, H. K., Grossman, S. R., McVean, G., Turnbaugh, P. J., Lander, E. S., Mitzenmacher, M., & Sabeti, P. C. (2011) · Science · doi:10.1126/science.1205438 · Cited by 3,345 · see citing works
The selectivity of protein kinase inhibitors: a further update
Bain, J., Plater, L., Elliott, M., Shpiro, N., Hastie, C. J., McLauchlan, H., Klevernic, I. V., Arthur, J. S. C., Alessi, D. R., & Cohen, P. (2007) · Biochemical Journal · doi:10.1042/bj20070797 · Cited by 2,522 · see citing works
A quantitative analysis of kinase inhibitor selectivity
Karaman, M. W., Herrgard, S., Treiber, D. K., Gallant, P., Atteridge, C. E., Campbell, B. T., Chan, K. W., Ciceri, P., Davis, M. I., Edeen, P. T., et al. (2008) · Nature Biotechnology · doi:10.1038/nbt1358 · Cited by 2,466 · see citing works
A postmodern moral tale: the ethics of research relationships
Somerville, M. (2002) · Nature reviews. Drug discovery · doi:10.1038/nrd773 · Cited by 2,175 · see citing works
A chemical method for fast and sensitive detection of DNA synthesis in vivo
Salic, A. N., & Mitchison, T. J. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0712168105 · Cited by 1,859 · see citing works
AMP-activated protein kinase induces a p53-dependent metabolic checkpoint
Jones, R. G., Plas, D. R., Kubek, S., Buzzai, M., Mu, J., Xu, Y., Birnbaum, M. J., & Thompson, C. B. (2005) · Molecular Cell · doi:10.1016/j.molcel.2005.03.027 · Cited by 1,619 · see citing works
Specificity and mechanism of action of some commonly used protein kinase inhibitors
Davies, S., Reddy, H., Caivano, M., & Cohen, P. (2000) · Biochemical Journal · doi:10.1042/0264-6021:3510095 · Cited by 1,618 · see citing works
The specificities of protein kinase inhibitors: an update
BAIN, J., McLAUCHLAN, H., ELLIOTT, M., & COHEN, P. (2003) · Biochemical Journal · doi:10.1042/bj20021535 · Cited by 1,369 · see citing works
Organelle isolation: functional mitochondria from mouse liver, muscle and cultured filroblasts
Frezza, C., Cipolat, S., & Scorrano, L. (2007) · Nature Protocols · doi:10.1038/nprot.2006.478 · Cited by 1,188 · see citing works
Rho‐kinase/ROCK: A key regulator of the cytoskeleton and cell polarity
Amano, M., Nakayama, M., & Kaibuchi, K. (2010) · Cytoskeleton · doi:10.1002/cm.20472 · Cited by 994 · see citing works
Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity
Anastassiadis, T., Deacon, S. W., Devarajan, K., Ma, H., & Peterson, J. R. (2011) · Nature Biotechnology · doi:10.1038/nbt.2017 · Cited by 919 · see citing works
Liang, J., Shao, S. H., Xu, Z.-X., Hennessy, B. T., Ding, Z., Larrea, M. D., Kondo, S., Dumont, D. J., Gutterman, J. U., Walker, C. L., et al. (2007) · Nature Cell Biology · doi:10.1038/ncb1537 · Cited by 868 · see citing works
Multidimensional Drug Profiling By Automated Microscopy
Perlman, Z. E., Slack, M. D., Feng, Y., Mitchison, T. J., Wu, L. F., & Altschuler, S. J. (2004) · Science · doi:10.1126/science.1100709 · Cited by 660 · see citing works
Lonard, D. M., Nawaz, Z., Smith, C. L., & O’Malley, B. W. (2000) · Molecular Cell · doi:10.1016/s1097-2765(00)80259-2 · Cited by 559 · see citing works
Structural Bioinformatics-Based Design of Selective, Irreversible Kinase Inhibitors
Cohen, M. S., Zhang, C., Shokat, K. M., & Taunton, J. (2005) · Science · doi:10.1126/science1108367 · Cited by 509 · see citing works
Wright, H. M., Clish, C. B., Mikami, T., Hauser, S., Yanagi, K., Hiramatsu, R., Serhan, C. N., & Spiegelman, B. M. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.3.1873 · Cited by 368 · see citing works
Jones, T. R., Carpenter, A. E., Lamprecht, M. R., Moffat, J., Silver, S. J., Grenier, J. K., Castoreno, A. B., Eggert, U., Root, D. E., Golland, P., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0808843106 · Cited by 368 · see citing works
Integrating high-content screening and ligand-target prediction to identify mechanism of action
Young, D. W., Bender, A., Hoyt, J., McWhinnie, E., Chirn, G.-W., Tao, C. Y., Tallarico, J. A., Labow, M., Jenkins, J. L., Mitchison, T. J., et al. (2008) · Nature Chemical Biology · doi:10.1038/nchembio.2007.53 · Cited by 345 · see citing works
Image-based multivariate profiling of drug responses from single cells
Loo, L., Wu, L. F., & Altschuler, S. J. (2007) · Nature Methods · doi:10.1038/nmeth1032 · Cited by 343 · see citing works
An Unbiased Cell Morphology–Based Screen for New, Biologically Active Small Molecules
Tanaka, M., Bateman, R. L., Rauh, D., Vaisberg, E. A., Ramachandani, S., Zhang, C., Hansen, K. C., Burlingame, A. L., Trautman, J. K., Shokat, K. M., et al. (2005) · PLoS Biology · doi:10.1371/journal.pbio.0030128 · Cited by 229 · see citing works
Protein kinase C-mediated regulation of the cell cycle
Jennifer, D. B. (2000) · Frontiers in bioscience · doi:10.2741/black · Cited by 151 · see citing works
The emerging power of chemical genetics
Specht, K. M., & Shokat, K. M. (2002) · Current Opinion in Cell Biology · doi:10.1016/s0955-0674(02)00317-4 · Cited by 119 · see citing works
Small‐Molecule Screening and Profiling by Using Automated Microscopy
Mitchison, T. J. (2004) · ChemBioChem · doi:10.1002/cbic.200400272 · Cited by 103 · see citing works
Vidau, C., González‐Polo, R. A., Niso‐Santano, M., Gómez‐Sánchez, R., Pedro, J. M. B., Pizarro‐Estrella, E., Blasco, R., Brunet, J., Belzunces, L., & Fuentes, J. M. (2011) · NeuroToxicology · doi:10.1016/j.neuro.2011.04.006 · Cited by 94 · see citing works
Schulze, C. J., Bray, W. M., Woerhmann, M. H., Stuart, J. M., Lokey, R. S., & Linington, R. G. (2013) · Chemistry & Biology · doi:10.1016/j.chembiol.2012.12.007 · Cited by 91 · see citing works
Self-citationBisphenol A diglycidyl ether (BADGE) is a PPARγ agonist in an ECV304 cell line
Bishop‐Bailey, D., Hla, T., & Warner, T. D. (2000) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0703628 · Cited by 68 · see citing works
de Cárcer, G. (2004) · Cancer Research · doi:10.1158/0008-5472.can-03-2214 · Cited by 66 · see citing works
Dennis, A. P., Lonard, D. M., Nawaz, Z., & O’Malley, B. W. (2005) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2004.11.009 · Cited by 59 · see citing works
Peach, K. C., Bray, W. M., Shikuma, N. J., Gassner, N. C., Lokey, R. S., Yildiz, F. H., & Linington, R. G. (2011) · Molecular BioSystems · doi:10.1039/c0mb00276c · Cited by 48 · see citing works
Self-citationSoltoff, S. P. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m305396200 · Cited by 39 · see citing works
Lyman, S. K., Crawley, S., Gong, R., Adamkewicz, J. I., McGrath, G., Chew, J. Y., Choi, J., Holst, C. R., Goon, L. H., Detmer, S. A., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0017692 · Cited by 36 · see citing works
Barros, S. D., Zakaroff‐Girard, A., Lafontan, M., Galitzky, J., & Bourlier, V. (2006) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.106.111849 · Cited by 31 · see citing works
Mitosis-arresting effect of the calcium channel inhibitor SK&F 96365 on human leukemia cells
Nordström, T., Nevanlinna, H. A., & Andersson, L. C. (1992) · Experimental Cell Research · doi:10.1016/0014-4827(92)90103-f · Cited by 29 · see citing works
Sutherland, J. J., Low, J. A., Blosser, W. D., Dowless, M. S., Engler, T. A., & Stancato, L. F. (2011) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-10-0720 · Cited by 29 · see citing works
Towne, D. L., Nicholl, E. E., Comess, K. M., Galasinski, S. C., Hajduk, P. J., & Abraham, V. C. (2012) · SLAS DISCOVERY · doi:10.1177/1087057112450050 · Cited by 22 · see citing works
Phenotypic Fingerprinting of Small Molecule Cell Cycle Kinase Inhibitors for Drug Discovery
Low, J. A., Chakravartty, A., Blosser, W. D., Dowless, M. S., Chalfant, C., Bragger, P., & Stancato, L. F. (2009) · Current Chemical Genomics · doi:10.2174/1875397300903010013 · Cited by 21 · see citing works
Cell-Cycle Inhibitor Profiling by High-Content Analysis
Gasparri, F., Ciavolella, A., & Galvani, A. P. (2007) · Springer eBooks · doi:10.1007/978-0-387-69116-9_13 · Cited by 20 · see citing works
Inhibition of Microtubule Polymerization by SK&F 96365, a Blocker of Receptor-Linked Ca2+ Entry
Mitsui‐Saito, M., Nakahata, N., & Ohizumi, Y. (2000) · The Japanese Journal of Pharmacology · doi:10.1254/jjp.82.269 · Cited by 8 · see citing works
Cytological profiling: providing more haystacks for chemists' needles.
Lorang, J., & King, R. W. (2005) · Genome biology · doi:10.1186/gb-2005-6-8-228 · Cited by 4 · see citing works
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Data-analysis strategies for image-based cell profiling
Caicedo, J. C., Cooper, S., Heigwer, F., Warchal, S., Qiu, P., Molnar, C., Vasilevich, A. S., Barry, J. D., Bansal, H. S., Kraus, O., et al. (2017) · Nature Methods · doi:10.1038/nmeth.4397 · Cited by 739 · see citing works
Image-based profiling for drug discovery: due for a machine-learning upgrade?
Chandrasekaran, S. N., Ceulemans, H., Boyd, J. D., & Carpenter, A. E. (2020) · Nature Reviews Drug Discovery · doi:10.1038/s41573-020-00117-w · Cited by 387 · see citing works
Nontargeted Metabolomics Reveals the Multilevel Response to Antibiotic Perturbations
Zampieri, M., Zimmermann, M., Claassen, M., & Sauer, U. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.04.002 · Cited by 188 · see citing works
Machine learning and image-based profiling in drug discovery
Scheeder, C., Heigwer, F., & Boutros, M. (2018) · Current Opinion in Systems Biology · doi:10.1016/j.coisb.2018.05.004 · Cited by 167 · see citing works
Applications in image-based profiling of perturbations
Caicedo, J. C., Singh, S., & Carpenter, A. E. (2016) · Current Opinion in Biotechnology · doi:10.1016/j.copbio.2016.04.003 · Cited by 166 · see citing works
Kurita, K. L., Glassey, E., & Linington, R. G. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1507743112 · Cited by 156 · see citing works
Self-citationCovington, B. C., MCLEAN, J. A. J., & Bachmann, B. O. (2016) · Natural Product Reports · doi:10.1039/c6np00048g · Cited by 150 · see citing works
Zampieri, M., Szappanos, B., Buchieri, M. V., Trauner, A., Piazza, I., Picotti, P., Gagneux, S., Borrell, S., Gicquel, B., Lelièvre, J., et al. (2018) · Science Translational Medicine · doi:10.1126/scitranslmed.aal3973 · Cited by 133 · see citing works
Advances in exploring the therapeutic potential of marine natural products
Liang, X., Luo, D., & Luesch, H. (2019) · Pharmacological Research · doi:10.1016/j.phrs.2019.104373 · Cited by 130 · see citing works
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Seal, S., Trapotsi, M., Spjuth, O., Singh, S., Puigvert, J. C., Greene, N., Bender, A., & Carpenter, A. E. (2024) · Nature Methods · doi:10.1038/s41592-024-02528-8 · Cited by 120 · see citing works
Mining prokaryotes for antimicrobial compounds: from diversity to function
Tracanna, V., de Jong, A., Medema, M. H., & Kuipers, O. P. (2017) · FEMS Microbiology Reviews · doi:10.1093/femsre/fux014 · Cited by 95 · see citing works
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Ziegler, S., Sievers, S., & Waldmann, H. (2021) · Cell chemical biology · doi:10.1016/j.chembiol.2021.02.012 · Cited by 82 · see citing works
Nyffeler, J., Willis, C., Harris, F. R., Foster, M. J., Chambers, B., Culbreth, M., Brockway, R. E., Davidson-Fritz, S., Dawson, D., Shah, I., et al. (2023) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2023.116513 · Cited by 67 · see citing works
Laraia, L., Garivet, G., Foley, D. J., Kaiser, N., Müller, S., Zinken, S., Pinkert, T., Wilke, J., Corkery, D., Pahl, A., et al. (2019) · Angewandte Chemie International Edition · doi:10.1002/anie.201913712 · Cited by 61 · see citing works
Akbarzadeh, M., Deipenwisch, I., Schoelermann, B., Pahl, A., Sievers, S., Ziegler, S., & Waldmann, H. (2021) · Cell chemical biology · doi:10.1016/j.chembiol.2021.12.009 · Cited by 51 · see citing works
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Harms, H., Kurita, K. L., Li, P., Wahome, P. G., He, H., Kinghorn, A. D., Carter, G. T., & Linington, R. G. (2016) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2016.09.008 · Cited by 48 · see citing works
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Rohban, M. H., Fuller, A. M., Tan, C., Goldstein, J. T., Syangtan, D., Gutnick, A., Devine, A., Nijsure, M. P., Rigby, M., Sacher, J. R., et al. (2022) · Cell Systems · doi:10.1016/j.cels.2022.08.003 · Cited by 37 · see citing works
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Phenotype-Guided Natural Products Discovery Using Cytological Profiling
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Self-citationMarine Mammal Microbiota Yields Novel Antibiotic with Potent Activity Against Clostridium difficile
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Schneidewind, T., Brause, A., Schölermann, B., Sievers, S., Pahl, A., Sankar, M. G., Winzker, M., Janning, P., Kumar, K., Ziegler, S., et al. (2021) · Cell chemical biology · doi:10.1016/j.chembiol.2021.06.003 · Cited by 28 · see citing works
High-throughput functional annotation of natural products by integrated activity profiling
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Self-citationWilke, J., Kawamura, T., Xu, H., Brause, A., Friese, A., Metz, M., Schepmann, D., Wünsch, B., Artacho-Cordón, A., Nieto, F. R., et al. (2021) · Cell chemical biology · doi:10.1016/j.chembiol.2021.01.009 · Cited by 24 · see citing works
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A statistical framework for high-content phenotypic profiling using cellular feature distributions
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“In addition, published studies tend to use a limited set of probes based on fl uorescent dyes or antibodies, which are usually combined into a single assay panel 17,19 – 21 .”
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Illuminating Dark Chemical Matter Using the Cell Painting Assay
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Lam, H. N., Lau, T. A., Lentz, A., Sherry, J., Cabrera-Cortez, A., Hug, K., Lalljie, A., Engel, J. N., Lokey, R. S., & Auerbuch, V. (2021) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01690-20 · Cited by 14 · see citing works
Self-citationLaraia, L., Garivet, G., Foley, D. J., Kaiser, N., Müller, S., Zinken, S., Pinkert, T., Wilke, J., Corkery, D., Pahl, A., et al. (2019) · Angewandte Chemie · doi:10.1002/ange.201913712 · Cited by 12 · see citing works
Wesseler, F., Lohmann, S., Riege, D., Halver, J., Roth, A., Pichlo, C., Weber, S., Takamiya, M., Müller, E., Ketzel, J., et al. (2022) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.2c01199 · Cited by 12 · see citing works
Wang, C., Yang, X., Mellick, G. D., & Feng, Y. (2016) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.6b00245 · Cited by 12 · see citing works
Theodore, C. M., Lorig‐Roach, N., Still, P. C., Johnson, T. A., Drašković, M., Schwochert, J. A., Naphen, C. N., Crews, M. S., Barker, S. A., Valeriote, F. A., et al. (2015) · Journal of Natural Products · doi:10.1021/np500840n · Cited by 11 · see citing works
Self-citationPahl, I., Pahl, A., Hauk, A., Budde, D., Sievers, S., Fruth, L., & Menzel, R. (2024) · Scientific Reports · doi:10.1038/s41598-024-55952-3 · Cited by 11 · see citing works
Martucci, H. F. H., Campit, S., Gee, S. R., Bray, W. M., Gokey, T., Cada, A. K., Yen, T., Minoura, K., Guliaev, A. B., Lokey, R. S., et al. (2017) · Journal of Natural Products · doi:10.1021/acs.jnatprod.6b00996 · Cited by 11 · see citing works
Self-citationGoebel, G. L., Giannino, N., Lampe, P., Qiu, X., Schloßhauer, J. L., Imig, J., Sievers, S., & Wu, P. (2024) · ChemBioChem · doi:10.1002/cbic.202400183 · Cited by 9 · see citing works
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Whitmarsh‐Everiss, T., Wang, Z., Hansen, C. H., Depta, L., Sassetti, E., Dan, O. R., Pahl, A., Sievers, S., & Laraia, L. (2023) · ChemBioChem · doi:10.1002/cbic.202200555 · Cited by 7 · see citing works
Zhao, Y., Liu, D. Y., Clark, T. N., Linington, R. G., & Kennelly, E. J. (2025) · Journal of Natural Products · doi:10.1021/acs.jnatprod.4c01458 · Cited by 6 · see citing works
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Baldo, F. (2019) · Physical Sciences Reviews · doi:10.1515/psr-2018-0115 · Cited by 5 · see citing works
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Lau, T. A., Bray, W. M., & Lokey, R. S. (2019) · Assay and Drug Development Technologies · doi:10.1089/adt.2018.894 · Cited by 4 · see citing works
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Balsamo, J. A., Thirman, H. L., Penton, K. E., Froese, J. T., Reisman, B. J., Lima, S. M., Hayes, M., Potts, C. R., Irish, J. M., Ferrell, P. B., et al. (2026) · RSC Chemical Biology · doi:10.1039/d5cb00203f · Cited by 2 · see citing works
Tabata, Y., Murai, N., Sasaki, T., Taniguchi, S., Suzuki, S., Yamazaki, K., & Ito, M. (2015) · SLAS DISCOVERY · doi:10.1177/1087057115598119 · Cited by 2 · see citing works
Cell Painting in activated cells illuminates phenotypic dark space and drug mechanisms of action
Zietek, M., Lohith, A., Terciano, D., Rabbitts, B. M., Khadilkar, A., MacMillan, J., & Lokey, R. S. (2026) · Nature Communications · doi:10.1038/s41467-026-76252-6 · Cited by 2 · see citing works
Self-citationBiswas, A., Greiner, L. C., Bonowski, J., Pahl, A., Sievers, S., Schmidt, A., Carsten Strohmann, B., Ziegler, S., Grigalunas, M., & Waldmann, H. (2025) · Helvetica Chimica Acta · doi:10.1002/hlca.202500155 · Cited by 1 · see citing works
Jiang, M., Hösle, D., Liu, Y., Sievers, S., & Wu, P. (2026) · JACS Au · doi:10.1021/jacsau.5c01600 · Cited by 1 · see citing works
Algorithm-driven, phenotype-directed bioactive molecular discovery
Piticari, A., Griggs, S. D., Crawford, L. A., Whittle, J., Mantilla, B. S., Sievers, S., Wright, M. H., Marsden, S. P., Basham, M., & Nelson, A. S. (2026) · Communications Chemistry · doi:10.1038/s42004-026-02066-8 · Cited by 1 · see citing works
Advancing antiviral strategies against emerging RNA viruses by phenotypic drug discovery
Tampere, M. (2021) · Figshare
MOAST: Mechanism of Action Similarity ToolPreprint
Lohith, A., Terciano, D., Murray, A., MacMillan, J. B., & Lokey, R. S. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.09.15.676411
Self-citationHigh content cell imaging reveals actin cytoskeleton-mediated control of the immunological synapse
German, Y. (2020) · theses.fr (ABES) · doi:10.70675/2e7a8371zbea8z4107zad46z604b32ec5fc1
Nonejuie, P., Samernate, T., Prasasti, F. F. T. A., Chaikeeratisak, V., & Pogliano, J. (2026) · Natural Product Reports · doi:10.1039/d6np00017g
Cellular Morphological Profiling of PROTAC Degraders of the m6A RNA Methyltransferase METTL3
Jiang, M., Chukwudi Thomas, U. G. W. U., Wortmann, L., Schloßhauer, J. L., Begemann, C., Sievers, S., Kliza, K. W., & Wu, P. (2026) · ACS Bio & Med Chem Au · doi:10.1021/acsbiomedchemau.6c00136
BindingDB Entry 50015692: Phenotypic Discovery of Triazolo[1,5-
BindingDB (2023) · UC San Diego · doi:10.7270/q2fx7fft
BindingDB Entry 50021192: Illuminating Dark Chemical Matter Using the Cell Painting Assay.
BindingDB (2025) · UC San Diego · doi:10.7270/q20869xg
- Authors
- Woehrmann, M. H., Bray, W. M., Durbin, J. K., Nisam, S. C., Michael, A. K., Glassey, E., Stuart, J. M., & Lokey, R. S.
- Affiliations
- University of California, Santa Cruz (US)
- Corresponding author
- Stuart, Joshua M
- Lokey, R. Scott
- Venue
- Molecular BioSystems
- Publisher
- Oxford University Press (OUP)
- Published
- 2013-08-20
- Volume
- 9
- Issue
- 11
- Pages
- 2604-2617
- ISSN
- 1742-2051 (ISSN-L)
- 1742-206X
- OpenAlex
- W1963836342
- Cited by
- 62
- References
- 41
- Citations by year
- 2026: 6 · 2025: 7 · 2024: 9 · 2023: 4 · 2022: 5 · 2021: 7 · 2020: 2 · 2019: 5 · 2018: 2 · 2017: 5 · 2016: 4 · 2015: 5 · 2014: 1
- FWCI
- 2.02
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular BioSystems (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of General Medical Sciences (R01GM084530)
- National Center for Research Resources (S10RR022455)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biophysics › Cell Image Analysis Techniques
- Physical Sciences › Computer Science › Computational Theory and Mathematics › Computational Drug Discovery Methods
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Keywords
- mechanism of action, bioactive compounds, image-based screening, microtubule poisons, Hsp90 inhibitors, proteasome inhibitors, mitochondrial uncoupling, PPARγ ligands, kinase inhibitors, kinase specificity, compound library screening
- MeSH terms
- Drug Evaluation, Preclinical, Humans, Microscopy, Phenotype, Reproducibility of Results, Informatics, Small Molecule Libraries, Drug Discovery, Molecular Imaging, High-Throughput Screening Assays, Automation, Laboratory
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