The discovery of first-in-class drugs: origins and evolution

Eder, Jörg; Sedrani, Richard; Wiesmann, Christian

doi:10.1038/nrd4336

Cited by 514Computational Drug Discovery MethodsHistorical Medical Research and TreatmentsPharmaceutical Economics and Policy

The discovery of first-in-class drugs: origins and evolution

Eder, Jörg, Sedrani, Richard, Wiesmann, Christian·2014·Nature Reviews Drug Discovery

DOI 10.1038/nrd4336

Open this paper in CoChat — free account

Abstract

Analysis of the origins of new drugs approved by the US Food and Drug Administration (FDA) from 1999 to 2008 suggested that phenotypic screening strategies had been more productive than target-based approaches in the discovery of first-in-class small-molecule drugs. However, given the relatively recent introduction of target-based approaches in the context of the long time frames of drug development, their full impact might not yet have become apparent. Here, we present an analysis of the origins of all 113 first-in-class drugs approved by the FDA from 1999 to 2013, which shows that the majority (78) were discovered through target-based approaches (45 small-molecule drugs and 33 biologics). In addition, of 33 drugs identified in the absence of a target hypothesis, 25 were found through a chemocentric approach in which compounds with known pharmacology served as the starting point, with only eight coming from what we define here as phenotypic screening: testing a large number of compounds in a target-agnostic assay that monitors phenotypic changes. We also discuss the implications for drug discovery strategies, including viewing phenotypic screening as a novel discipline rather than as a neoclassical approach.

Integrity signals

Registry

Crossref · 10.1038/nrd4336

Cites

64 of 64 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Identification of the molecular target and selection of a promising candidate from a list of toxic compounds remains a challenge for phenotypic screens.
“Still, identification of the molecular target and selection of a promising candidate from a list of toxic compounds remains a challenge for phenotypic screens (Eder et al., 2014).”
From Degradation of CCNK/CDK12 is a druggable vulnerability of colorectal cancer (2021) · cites this paper as Eder et al., 2014

Tumor angiogenesis: therapeutic implications
Sherwood, L. M., Parris, E. E., & Folkman, J. (1971) · New England Journal of Medicine · doi:10.1056/nejm197111182852108 · Cited by 10,187 · see citing works
Vascular Endothelial Growth Factor Is a Secreted Angiogenic Mitogen
Leung, D. W., Cachianes, G., Kuang, W.-J., Goeddel, D. V., & Ferrara, N. (1989) · Science · doi:10.1126/science.2479986 · Cited by 4,988 · see citing works
A New Consistent Chromosomal Abnormality in Chronic Myelogenous Leukaemia identified by Quinacrine Fluorescence and Giemsa Staining
ROWLEY, J. D. (1973) · Nature · doi:10.1038/243290a0 · Cited by 4,291 · see citing works
Selective inhibition of BET bromodomains
Filippakopoulos, P., Qi, J., Picaud, S., Shen, Y., Smith, W. B., Fedorov, O., Morse, E. M., Keates, T., Hickman, T. T., Felletar, I., et al. (2010) · Nature · doi:10.1038/nature09504 · Cited by 4,262 · see citing works
Can the pharmaceutical industry reduce attrition rates?
Kola, I., & Landis, J. (2004) · Nature Reviews Drug Discovery · doi:10.1038/nrd1470 · Cited by 4,167 · see citing works
Tumor Cells Secrete a Vascular Permeability Factor That Promotes Accumulation of Ascites Fluid
Senger, D. R., Galli, S. J., Dvořàk, A. M., Perruzzi, C. A., Harvey, V. S., & Dvorak, H. F. (1983) · Science · doi:10.1126/science.6823562 · Cited by 3,969 · see citing works
How to improve R&D productivity: the pharmaceutical industry's grand challenge
Paul, S. M., Mytelka, D. S., Dunwiddie, C. T., Persinger, C. C., Munos, B. H., Lindborg, S. R., & Schacht, A. L. (2010) · Nature Reviews Drug Discovery · doi:10.1038/nrd3078 · Cited by 3,566 · see citing works
The druggable genome
Hopkins, A. L., & Groom, C. R. (2002) · Nature Reviews Drug Discovery · doi:10.1038/nrd892 · Cited by 3,305 · see citing works
Transplacental Carcinogenesis by Stilbestrol
Folkman, J. (1971) · New England Journal of Medicine · doi:10.1056/nejm197108122850711 · Cited by 2,640 · see citing works
Drugs for bad bugs: confronting the challenges of antibacterial discovery
Payne, D. J., Gwynn, M. N., Holmes, D. J., & Pompliano, D. L. (2007) · Nature Reviews Drug Discovery · doi:10.1038/nrd2201 · Cited by 2,512 · see citing works
A minute chromosome in human chronic granulocytic leukemia
Nowell̀, P. C. (1960) · Science · Cited by 2,316 · see citing works
Targets for Cell Cycle Arrest by the Immunosuppressant Rapamycin in Yeast
Heitman, J., Movva, N. R., & Hall, M. N. (1991) · Science · doi:10.1126/science.1715094 · Cited by 2,010 · see citing works
Diagnosing the decline in pharmaceutical R&D efficiency
Scannell, J. W., Blanckley, A., Boldon, H., & Warrington, B. (2012) · Nature Reviews Drug Discovery · doi:10.1038/nrd3681 · Cited by 1,981 · see citing works
How were new medicines discovered?
Swinney, D. C., & Anthony, J. (2011) · Nature Reviews Drug Discovery · doi:10.1038/nrd3480 · Cited by 1,812 · see citing works
Humanization of an anti-vascular endothelial growth factor monoclonal antibody for the therapy of solid tumors and other disorders.
Presta, L. G., Chen, H., O'Connor, S. J., Chisholm, V., Meng, Y. G., KRUMMEN, L. A., Winkler, M., & Ferrara, N. (1997) · PubMed · Cited by 1,602 · see citing works
Fused transcript of abl and bcr genes in chronic myelogenous leukaemia
Shtivelman, E., Lifshitz, B., Gale, R. P., & Canaani, E. (1985) · Nature · doi:10.1038/315550a0 · Cited by 1,583 · see citing works
Small molecule–mediated disruption of Wnt-dependent signaling in tissue regeneration and cancer
Chen, B., Dodge, M. E., Tang, W., Lü, J., Ma, Z., Fan, C.-W., Wei, S., Hao, W., Kilgore, J. A., Williams, N. S., et al. (2009) · Nature Chemical Biology · doi:10.1038/nchembio.137 · Cited by 1,385 · see citing works
Impact of high-throughput screening in biomedical research
Macarron, R., Banks, M. N., Bojanic, D., Burns, D. J., Cirovic, D. A., Garyantes, T., Green, D. V. S., Hertzberg, R. P., Janzen, W. P., Paslay, J. W., et al. (2011) · Nature Reviews Drug Discovery · doi:10.1038/nrd3368 · Cited by 1,364 · see citing works
Spiroindolones, a Potent Compound Class for the Treatment of Malaria
Rottmann, M., McNamara, C. W., Yeung, B. K. S., Lee, M., Zou, B., Russell, B., Seitz, P., Plouffe, D., Dharia, N. V., Tan, J., et al. (2010) · Science · doi:10.1126/science.1193225 · Cited by 1,212 · see citing works
Lessons from 60 years of pharmaceutical innovation
Munos, B. H. (2009) · Nature Reviews Drug Discovery · doi:10.1038/nrd2961 · Cited by 1,208 · see citing works
PTC124 targets genetic disorders caused by nonsense mutations
Welch, E. M., Barton, E. R., Zhuo, J., Tomizawa, Y., Friesen, W. J., Trifillis, P., Paushkin, S. V., Patel, M., Trotta, C. R., Hwang, S., et al. (2007) · Nature · doi:10.1038/nature05756 · Cited by 1,138 · see citing works
Inhibition of the Abl protein-tyrosine kinase in vitro and in vivo by a 2-phenylaminopyrimidine derivative.
Buchdunger, E., Zimmermann, J., Mett, H., Meyer, T., Müller, M., Druker, B. J., & Lydon, N. (1996) · PubMed · Cited by 1,060 · see citing works
Chemical genetics strategy identifies an HCV NS5A inhibitor with a potent clinical effect
Gao, M., Nettles, R. E., Belema, M., Snyder, L. B., Nguyen, V. N., Fridell, R. A., Serrano‐Wu, M. H., Langley, D. R., Sun, J.-H., O’Boyle, D. R., et al. (2010) · Nature · doi:10.1038/nature08960 · Cited by 941 · see citing works
Varenicline: An α4β2 Nicotinic Receptor Partial Agonist for Smoking Cessation
Coe, J. W., Brooks, P. R., Vetelino, M. G., Wirtz, M. C., Arnold, E. P., Huang, J., Sands, S. B., Davis, T. I., Lebel, L. A., Fox, C. B., et al. (2005) · Journal of Medicinal Chemistry · doi:10.1021/jm050069n · Cited by 930 · see citing works
The productivity crisis in pharmaceutical R&D
Pammolli, F., Magazzini, L., & Riccaboni, M. (2011) · Nature Reviews Drug Discovery · doi:10.1038/nrd3405 · Cited by 918 · see citing works
Strategies and challenges for the next generation of therapeutic antibodies
Beck, A., Wurch, T., Bailly, C., & Corvaı̈a, N. (2010) · Nature reviews. Immunology · doi:10.1038/nri2747 · Cited by 851 · see citing works
Vasculae Reactions of Normal and Malignant Tissues in Vivo. I. Vascular Reactions of Mice to Wounds and to Normal and Neoplastic Transplants
Algire, G. H., Chalkley, H. W., Legallais, F. Y., & Park, H. D. (1945) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/6.1.73 · Cited by 472 · see citing works
Drug Discovery
Sneader, W. (2005) · Wiley eBooks · doi:10.1002/0470015535 · Cited by 428 · see citing works
Phenotypic screens as a renewed approach for drug discovery
Zheng, W., Thorne, N., & McKew, J. C. (2013) · Drug Discovery Today · doi:10.1016/j.drudis.2013.07.001 · Cited by 421 · see citing works
Phenotypic vs. Target-Based Drug Discovery for First-in-Class Medicines
Swinney, D. C. (2013) · Clinical Pharmacology & Therapeutics · doi:10.1038/clpt.2012.236 · Cited by 417 · see citing works
Reporter gene technology: the future looks bright
Naylor, L. H. (1999) · Biochemical Pharmacology · doi:10.1016/s0006-2952(99)00096-9 · Cited by 344 · see citing works
Drug Discovery: A History
Sneader, W. (2005) · Cited by 290 · see citing works
Tumor Angiogenesis: Transfilter Diffusion Studies in the Hamster by the Transparent Chamber Technique 2
Greenblatt, M., & Shubi, P. (1968) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/41.1.111 · Cited by 283 · see citing works
Can cell systems biology rescue drug discovery?
Butcher, E. C. (2005) · Nature Reviews Drug Discovery · doi:10.1038/nrd1754 · Cited by 277 · see citing works
Antitumor Activity of 3-Ingenyl Angelate
Ogbourne, S. M., Suhrbier, A., Jones, B., et al. (2004) · Cancer Research · doi:10.1158/0008-5472.can-03-2837 · Cited by 256 · see citing works
2-Azetidinones as Inhibitors of Cholesterol Absorption
Burnett, D. A., Caplen, M. A., Davis, H. R., et al. (1994) · Journal of Medicinal Chemistry · doi:10.1021/jm00038a001 · Cited by 239 · see citing works
Rebuilding the R&D engine in big pharma.
Garnier, J.-P. (2008) · PubMed · Cited by 227 · see citing works
A new grammar for drug discovery
Fishman, M. C., & Porter, J. A. (2005) · Nature · doi:10.1038/437491a · Cited by 193 · see citing works
Modern Phenotypic Drug Discovery Is a Viable, Neoclassic Pharma Strategy
Lee, J. A., Uhlik, M. T., Moxham, C. M., Tomandl, D., & Sall, D. J. (2012) · Journal of Medicinal Chemistry · doi:10.1021/jm201649s · Cited by 190 · see citing works
Drug Development: The role of innovation in drug development
Drews, J., & Ryser, S. (1997) · Nature Biotechnology · doi:10.1038/nbt1297-1318 · Cited by 179 · see citing works
Deoxyguanosine toxicity in a mouse T lymphoma: Relationship to purine nucleoside phosphorylase-associated immune dysfunction
Gudas, L. J., Ullman, B., Cohen, A. M., et al. (1978) · Cell · doi:10.1016/0092-8674(78)90239-8 · Cited by 144 · see citing works
Transport and Phosphorylation as Factors in the Antitumor Action of Cytosine Arabinoside
Kessel, D. H., Hall, T. C., & Wodinsky, I. (1967) · Science · doi:10.1126/science.156.3779.1240 · Cited by 127 · see citing works
Neoclassic Drug Discovery: The Case for Lead Generation Using Phenotypic and Functional Approaches
Lee, J. A., & Berg, E. L. (2013) · SLAS DISCOVERY · doi:10.1177/1087057113506118 · Cited by 125 · see citing works
Finding novel pharmaceuticals in the systems biology era using multiple effective drug targets, phenotypic screening and knowledge of transporters: where drug discovery went wrong and how to fix it
Kell, D. B. (2013) · FEBS Journal · doi:10.1111/febs.12268 · Cited by 120 · see citing works
Effects of 2,4-diaminoquinazoline derivatives on SMN expression and phenotype in a mouse model for spinal muscular atrophy
Butchbach, M. E. R., Singh, J., Þorsteinsdóttir, M., Saieva, L., Slominski, E., Thurmond, J., Andrésson, Þ., Zhang, J., Edwards, J. D., Simard, L. R., et al. (2009) · Human Molecular Genetics · doi:10.1093/hmg/ddp510 · Cited by 119 · see citing works
Antiviral activity of 1-docosanol, an inhibitor of lipid-enveloped viruses including herpes simplex.
Katz, D. H., Marcelletti, J. F., Khalil, M., Pope, L. E., & Katz, L. R. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.23.10825 · Cited by 109 · see citing works
From toxicological problem to therapeutic use: The discovery of the mode of action of 2‐(2‐nitro‐4‐trifluoromethylbenzoyl)‐1,3‐cyclohexanedione (NTBC), its toxicology and development as a drug
Lock, E. A., Ellis, M. K., Gaskin, P., Robinson, M., Auton, T. R., Provan, W. M., Smith, L. L., Prisbylla, M. P., Mutter, L. C., & Lee, D. L. (1998) · Journal of Inherited Metabolic Disease · doi:10.1023/a:1005458703363 · Cited by 108 · see citing works
Forward chemical genetics: progress and obstacles on the path to a new pharmacopoeia
Lokey, R. S. (2003) · Current Opinion in Chemical Biology · doi:10.1016/s1367-5931(02)00002-9 · Cited by 106 · see citing works
Pharmaceutical R&D: the road to positive returns
David, E., Tramontin, T., & Zemmel, R. W. (2009) · Nature Reviews Drug Discovery · doi:10.1038/nrd2948 · Cited by 96 · see citing works
Is poor research the cause of the declining productivity of the pharmaceutical industry? An industry in need of a paradigm shift
Sams‐Dodd, F. (2012) · Drug Discovery Today · doi:10.1016/j.drudis.2012.10.010 · Cited by 94 · see citing works
2-Amino-6-methoxypurine arabinoside: an agent for T-cell malignancies.
Lambe, C. U., Averett, D. R., Paff, M. T., Reardon, J. E., Wilson, J. G., & Krenitsky, T. A. (1995) · PubMed · Cited by 93 · see citing works
Selective toxicity of deoxyguanosine and arabinosyl guanine for T- leukemic cells
Cohen, A., Lee, J., & Gelfand, E. W. (1983) · Blood · doi:10.1182/blood.v61.4.660.660 · Cited by 92 · see citing works
Realism in drug discovery—could Cassandra be right?
Horrobin, D. F. (2001) · Nature Biotechnology · doi:10.1038/nbt1201-1099 · Cited by 77 · see citing works
Flupirtine, a re-discovered drug, revisited
Szelenyi, I. (2013) · Inflammation Research · doi:10.1007/s00011-013-0592-5 · Cited by 69 · see citing works
A critique of the molecular target-based drug discovery paradigm based on principles of metabolic control: Advantages of pathway-based discovery
Hellerstein, M. K. (2007) · Metabolic Engineering · doi:10.1016/j.ymben.2007.09.003 · Cited by 56 · see citing works
The case for entrepreneurship in R&D in the pharmaceutical industry
Douglas, F. L., Narayanan, V. K., Mitchell, L., et al. (2010) · Nature Reviews Drug Discovery · doi:10.1038/nrd3230 · Cited by 46 · see citing works
Back to the Future: Lessons Learned in Modern Target-based and Whole-Cell Lead Optimization of Antimalarials
Chatterjee, A. K., & Yeung, B. K. S. (2012) · Current Topics in Medicinal Chemistry · doi:10.2174/156802612799362977 · Cited by 46 · see citing works
Chemoproteomics-driven drug discovery: addressing high attrition rates
Hall, S. E. (2006) · Drug Discovery Today · doi:10.1016/j.drudis.2006.04.014 · Cited by 36 · see citing works
Why has R&D productivity declined in the pharmaceutical industry?
Ruffolo, R. R., Jr. (2006) · Expert Opinion on Drug Discovery · doi:10.1517/17460441.1.2.99 · Cited by 36 · see citing works
Systems and integrative biology as alternative guises for pharmacology: Prime time for an iPharm concept?
Williams, M. J. (2005) · Biochemical Pharmacology · doi:10.1016/j.bcp.2005.08.019 · Cited by 29 · see citing works
Phenotypic Screening Strategies for Neurodegenerative Diseases: A Pathway to Discover Novel Drug Candidates and Potential Disease Targets or Mechanisms
Pruss, R. M. (2010) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/187152710793237377 · Cited by 23 · see citing works
Combining imaging and pathway profiling: an alternative approach to cancer drug discovery
Carragher, N. O., Brunton, V. G., & Frame, M. C. (2012) · Drug Discovery Today · doi:10.1016/j.drudis.2012.02.002 · Cited by 20 · see citing works
Forward Chemical Genetics in Yeast for Discovery of Chemical Probes Targeting Metabolism
St.Onge, R., Schlecht, U., Scharfe, C., & Evangelista, M. (2012) · Molecules · doi:10.3390/molecules171113098 · Cited by 19 · see citing works
Protein Reporter Bioassay Systems for the Phenotypic Screening of Candidate Drugs: A Mouse Platform for Anti-Aging Drug Screening
Chiba, T., Tsuchiya, T., Mori, R., et al. (2012) · Sensors · doi:10.3390/s120201648 · Cited by 15 · see citing works

Flagged first, then by citations

Sorted by citations

A comprehensive map of molecular drug targets
Santos, R., Ursu, O., Gaulton, A., Bento, A. P., Donadi, R. S., Bologa, C. G., Karlsson, A., Al-Lazikani, B., Hersey, A., Oprea, T. I., et al. (2017) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2016.230 · Cited by 2,427 · see citing works
Opportunities and challenges in phenotypic drug discovery: an industry perspective
Moffat, J. G., Vincent, F., Lee, J. A., Eder, J., & Prunotto, M. (2017) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2017.111 · Cited by 939 · see citing works
Self-citation
Screening out irrelevant cell-based models of disease
Horvath, P., Aulner, N., Bickle, M., Davies, A. M., Nery, E. D., Ebner, D., Montoya, M. C., Östling, P., Pietiäinen, V., Price, L. S., et al. (2016) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2016.175 · Cited by 525 · see citing works
Utilizing graph machine learning within drug discovery and development
Gaudelet, T., Day, B., Jamasb, A. R., Soman, J., Regep, C., Liu, G., Hayter, J. B. R., Vickers, R., Roberts, C., Tang, J., et al. (2021) · Briefings in Bioinformatics · doi:10.1093/bib/bbab159 · Cited by 313 · see citing works
Drug discovery and development for rare genetic disorders
Sun, W., Zheng, W., & Simeonov, A. (2017) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.38326 · Cited by 107 · see citing works
Degradation of CCNK/CDK12 is a druggable vulnerability of colorectal cancer
Dieter, S. M., Siegl, C., Codó, P. L., Huerta, M., Ostermann-Parucha, A. L., Schulz, E., Zowada, M. K., Martin, S., Laaber, K., Nowrouzi, A., et al. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.109394 · Cited by 95 · see citing works
Machine Learning Models and Pathway Genome Data Base for Trypanosoma cruzi Drug Discovery
Ekins, S., Lage de Siqueira-Neto, J., McCall, L.-I., Sarker, M., Yadav, M., Ponder, E. L., Kallel, E. A., Kellar, D., Chen, S., Arkin, M., et al. (2015) · PLOS Neglected Tropical Diseases · doi:10.1371/journal.pntd.0003878 · Cited by 93 · see citing works
The current landscape of 3D in vitro tumor models: what cancer hallmarks are accessible for drug discovery?
Rodenhizer, D., Dean, T., D'Arcangelo, E., & McGuigan, A. P. (2018) · Advanced Healthcare Materials · doi:10.1002/adhm.201701174 · Cited by 80 · see citing works
High-content phenotypic and pathway profiling to advance drug discovery in diseases of unmet need
Hughes, R. E., Elliott, R. J. R., Dawson, J. C., & Carragher, N. O. (2021) · Cell Chemical Biology · doi:10.1016/j.chembiol.2021.02.015 · Cited by 62 · see citing works
Essential Medicinal Chemistry of Essential Medicines
Serafini, M., Cargnin, S., Massarotti, A., Pirali, T., & Genazzani, A. A. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c00415 · Cited by 46 · see citing works
Integrated, automated maintenance, expansion and differentiation of 2D and 3D patient-derived cellular models for high throughput drug screening
Boussaad, I., Cruciani, G., Bolognin, S., Antony, P., Dording, C. M., Kwon, Y.-J., Heutink, P., Fava, E., Schwamborn, J. C., & Krüger, R. (2021) · Scientific Reports · doi:10.1038/s41598-021-81129-3 · Cited by 42 · see citing works
Representing high throughput expression profiles via perturbation barcodes reveals compound targets
Filzen, T. M., Kutchukian, P. S., Hermes, J. D., Li, J., & Tudor, M. (2017) · PLOS Computational Biology · doi:10.1371/journal.pcbi.1005335 · Cited by 31 · see citing works
Expanding therapeutic opportunities for neurodegenerative diseases: A perspective on the important role of phenotypic screening
Swalley, S. E. (2020) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2019.115239 · Cited by 24 · see citing works
Landscape of Innovation for Cardiovascular Pharmaceuticals: From Basic Science to New Molecular Entities
Beierlein, J. M., McNamee, L. M., Walsh, M. J., Kaitin, K. I., DiMasi, J. A., & Ledley, F. D. (2017) · Clinical Therapeutics · doi:10.1016/j.clinthera.2017.06.001 · Cited by 24 · see citing works

Approaches to Protozoan Drug Discovery: Phenotypic Screening
Sykes, M. L., & Avery, V. M. (2013) · Journal of Medicinal Chemistry · doi:10.1021/jm4004279 · Cited by 76 · see citing works
Applications of chemogenomic library screening in drug discovery
Jones, L. H., & Bunnage, M. E. (2017) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2016.244 · Cited by 192 · see citing works
Drug Discovery Paradigms: Phenotypic-Based Drug Discovery
Talevi, A., & Bellera, C. L. (2022) · Computer-aided drug discovery and design · doi:10.1007/978-3-030-95895-4_2 · Cited by 2 · see citing works
The Resurrection of Phenotypic Drug Discovery
Childers, W. E., Elokely, K. M., & Abou-Gharbia, M. A. (2020) · ACS Medicinal Chemistry Letters · doi:10.1021/acsmedchemlett.0c00006 · Cited by 45 · see citing works
Phenotypic approaches to small-molecule discovery in chemical biology
Wagner, B. K., & Dey, M. (2021) · Cell chemical biology · doi:10.1016/j.chembiol.2021.02.018

Authors: Eder, J., Sedrani, R., & Wiesmann, C.
Affiliations: Novartis (Switzerland) (CH)
Corresponding author: Eder, Jörg
ORCID: Eder, Jörg
Sedrani, Richard
Wiesmann, Christian
Venue: Nature Reviews Drug Discovery
Publisher: Springer Science and Business Media LLC
Published: 2014-07-18
Volume: 13
Issue: 8
Pages: 577-587
ISSN: 1474-1776 (ISSN-L)
1474-1784
DOI: 10.1038/nrd4336
OpenAlex: W2060333462
Cited by: 514
References: 64
Citations by year: 2026: 29 · 2025: 28 · 2024: 49 · 2023: 39 · 2022: 36 · 2021: 50 · 2020: 54 · 2019: 48 · 2018: 36 · 2017: 52 · 2016: 48 · 2015: 37 · 2014: 8
FWCI: 4.03
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature Reviews Drug Discovery (publishedVersion)
PubMed (publishedVersion)
Funders: Novartis Institutes for BioMedical Research
Topics: Physical Sciences › Computer Science › Computational Theory and Mathematics › Computational Drug Discovery Methods
Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Historical Medical Research and Treatments
Social Sciences › Economics, Econometrics and Finance › Economics and Econometrics › Pharmaceutical Economics and Policy
Keywords: first-in-class drugs, drug discovery strategies, phenotypic screening, target-based drug discovery, small molecule drugs, biologics, FDA-approved drugs, drug development history
MeSH terms: Drug Industry, Drug Evaluation, Preclinical, Humans, Drug Approval, Systems Biology, History, 20th Century, History, 21st Century, Drug Discovery

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

The discovery of first-in-class drugs: origins and evolution

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Cites

Cited by

Related

Record

About these checks