Portal de Periódicos da CAPES

The Academic Pill: How Academia Contributes to Curing Diseases

2019; Elsevier BV; Volume: 24; Issue: 3 Linguagem: Inglês

10.1177/2472555218824280

2472-5560

Marc Bickle,

Genetics, Bioinformatics, and Biomedical Research

This special issue of SLAS Discovery showcases academic screening centers and not-for-profit translational drug discovery centers. Historically, high-throughput screening was developed by the pharmaceutical industry and until the end of the 20th century was mainly carried out within its walls. After the sequencing of the human genome, academic institutions started creating screening centers to either find tool compounds or carry out RNA interference screens to study the genome. In 2003, the U.S. National Institutes of Health (NIH) Roadmap set out a plan for creating screening centers and chemical libraries, further strengthening the trend of academic screening.1Zerhouni E. The NIH Roadmap.Science. 2003; 302: 63Google Scholar Although many academic screening centers aim to discover tool compounds for chemical biology, an appetite has always existed for more translational projects; academic screening would hopefully produce therapeutic molecules that could be used in the clinic. The desire for novel therapeutic molecules was particularly strong for neglected and rare diseases, where a lack of economic incentive meant that therapies were not available. Like many trends, after an initial enthusiasm there came a realization that developing new drugs was challenging and that academic screening centers, while facing different difficulties compared with industrial screening laboratories, also struggled to bring drugs into the clinic. The reasons for this struggle are numerous, but I would like to underline two major reasons. First, there is a lack of funding opportunities for bringing hit compounds forward and developing lead candidates into drug candidates. Public research funds typically do not finance such work, since it is not basic research, and the projects are at too early a stage for applying for translational grants to spin out a company. It is equally hard to find pharmaceutical partners at this stage. Typically, the pharmaceutical industry invests in projects where a proof of principle has been obtained in animals, and the effects of the molecule of interest are better understood. Second, academic screening centers typically lack the infrastructure to host, curate, and process very large, high-quality chemical collections. Given the importance of the quality of compounds entering the screening process, it is perhaps not surprising that many projects did not materialize into lead molecules that could be brought forward into the clinic. To fill the gap between academic research and drug development, translational drug discovery centers were established. These centers were created to help bridge academia and industry; to have the critical mass in terms of people, instruments, compounds, and chemistry; and to form private–public partnerships (PPPs) to bring innovative compounds forward into the clinic. This special issue of SLAS Discovery offers a snapshot of the research being conducted in academic screening laboratories and in translational drug discovery centers. We invited many centers to contribute and 15 laboratories answered the call. As to be expected, the 15 manuscripts submitted cover a wide range of topics. The first three manuscripts, by Franke et al.,2Franke R. Hinkelmann B. Fetz V. et al.xCELLanalyzer: A Framework for the Analysis of Cellular Impedance Measurements for Mode of Action Discovery.SLAS Discov. 2019; 24: 213-223Google Scholar Warchal et al.,3Warchal S.J. Dawson J.C. Carragher N.O. Evaluation of Machine Learning Classifiers to Predict Compound Mechanism of Action When Transferred across Distinct Cell Lines.SLAS Discov. 2019; 24: 224-233Google Scholar and Janosch et al.,4Janosch A. Kaffka C. Bickle M. Unbiased Phenotype Detection Using Negative Controls.SLAS Discov. 2019; 24: 234-241Google Scholar describe analytical methods for phenotypic profiling of cellular responses. Using phenotypic signatures for discovering the mode of action of compounds is a very active research field, and it is not surprising to see that all three analytical articles focus on that subject. The manuscripts of Starkuviene et al.,5Starkuviene V. Kallenberger S.M. Beil N. et al.High-Density Cell Arrays for Genome-Scale Phenotypic Screening.SLAS Discov. 2019; 24: 274-283Google Scholar Imamura et al.,6Imamura R.M. Kumagai K. Nakano H. et al.Inexpensive High-Throughput Screening of Kinase Inhibitors Using One-Step Enzyme-Coupled Fluorescence Assay for ADP Detection.SLAS Discov. 2019; 24: 284-294Google Scholar Colussi et al.,7Colussi D.J. Jacobson M.A. Patient-Derived Phenotypic High-Throughput Assay to Identify Small Molecules Restoring Lysosomal Function in Tay–Sachs Disease.SLAS Discov. 2019; 24: 295-303Google Scholar Close et al.,8Close D.A. Wang A.X. Kochanek S.J. et al.Implementation of the NCI-60 Human Tumor Cell Line Panel to Screen 2260 Cancer Drug Combinations to Generate >3 Million Data Points Used to Populate a Large Matrix of Anti-Neoplastic Agent Combinations (ALMANAC) Database.SLAS Discov. 2019; 24: 242-263Google Scholar Siva et al.,9Siva K. Ek F. Chen J. et al.A Phenotypic Screening Assay Identifies Modulators of Diamond Blackfan Anemia.SLAS Discov. 2019; 24: 304-313Google Scholar and Wiseman et al.10Wiseman E. Zamuner A. Tang Z. et al.Integrated Multiparametric High-Content Profiling of Endothelial Cells.SLAS Discov. 2019; 24: 264-273Google Scholar all describe novel model systems, assays, and technologies that allow the screening of large collections of molecules. This illustrates that academia is a rich source for novel assays as basic research is transformed into screens, leading to unexplored therapeutic avenues. Lastly, Baillargeon et al.,11Baillargeon P. Fernandez-Vega V. Sridharan B.P. et al.The Scripps Molecular Screening Center and Translation Research Institute.SLAS Discov. 2019; 24: 386-397Google Scholar Moraes et al.,12Moraes C.B. Witt G. Kuzikov M. et al.Accelerating Drug Discovery Efforts for Trypanosomatidic Infections Using an Integrated Transnational Academic Drug Discovery Platform.SLAS Discov. 2019; 24: 346-361Google Scholar Otvos et al.,13Otvos R.A. Still K.B.M. Somsen G.W. et al.Drug Discovery on Natural Products: From Ion Channels to nAChRs, from Nature to Libraries, from Analytics to Assays.SLAS Discov. 2019; 24: 362-385Google Scholar D’Agostino et al.,14D’Agostino V.G. Sighel D. Zucal C. et al.Screening Approaches for Targeting Ribonucleoprotein Complexes: A New Dimension for Drug Discovery.SLAS Discov. 2019; 24: 314-331Google Scholar Birchall et al.,15Birchall K. Merritt A. Sattikar A. et al.Design of the LifeArc Index Set and Retrospective Review of Its Performance: A Collection for Sharing.SLAS Discov. 2019; 24: 332-345Google Scholar and Brennecke et al.16Brennecke P. Rasina D. Aubi O. et al.EU-OPENSCREEN: A Novel Collaborative Approach to Facilitate Chemical Biology.SLAS Discov. 2019; 24: 398-413Google Scholar are reviews of the screening efforts of screening laboratories and their networks, covering a wide range of applications. These reviews showcase how expertise in different fields allows academic projects to progress toward the clinic. The 15 laboratories that contributed to this special issue all have individual expertise and operational modes, as summarized below. The Helmholtz Centre for Infection Research (HZI) in Braunschweig, Germany, started its operations in 2006, although its predecessor institute was founded in 1965.2Franke R. Hinkelmann B. Fetz V. et al.xCELLanalyzer: A Framework for the Analysis of Cellular Impedance Measurements for Mode of Action Discovery.SLAS Discov. 2019; 24: 213-223Google Scholar The institute currently has 822 employees, and the three main goals of the Chemical Biology (CBIO) Department are discovering new antibacterial and antiviral drugs, characterizing their functionality, and optimizing their properties. CBIO focuses on infection research and small molecules that can function as antimicrobial or antiviral agents, interfere with pathogenicity factors, or stimulate the immune system. The discovery of new drugs includes the development of innovative, mainly phenotypic screening assays for medium-throughput screening campaigns. At the department’s disposal are approximately 30,000 compounds, of which the proprietary HZI natural product collection and a proprietary academic collection (approximately 4000 compounds) are specific features. The department is actively involved in several projects of the German Centre for Infection Research (DZIF), in the Translational Unit “Antibiotics” and the Translational Infrastructure “Antivirals.” Screening is conducted either at the HZI or at an external partner site. A medium- to high-throughput screen under biological safety level S3 or S1 conditions can be performed with a robotic pipetting system. Antibacterial or antiviral screens under S2 conditions will become operative in H1/2019. Identified active compounds are profiled against the ESKAPE panel of bacterial pathogens and against mammalian cell lines to determine the selectivity index. For mode of action studies, various functional and profiling methods are established to characterize the effect of the compounds on the target pathogen or cell line. These include membrane potential and membrane permeability, high-content imaging, impedance spectroscopy,2Franke R. Hinkelmann B. Fetz V. et al.xCELLanalyzer: A Framework for the Analysis of Cellular Impedance Measurements for Mode of Action Discovery.SLAS Discov. 2019; 24: 213-223Google Scholar transcriptomics, targeted and untargeted metabolomics, and peptide arrays as the main “omics” technologies. Specific technologies for studying the uptake of compounds in gram-negative bacteria have been established. The department also has synthetic chemistry capabilities (approximately 12 FTE) that deal with lead generation and lead optimization by synthesis. In addition to de novo-designed drug conjugates and natural product-based lead optimization, the team advances screening actives to hit series. The most promising compounds are profiled in vivo in the animal facility of the HZI, where mouse models to study the pharmacokinetic (PK) and pharmacodynamic (PD) parameters of advanced compounds in antibacterial or antiviral infection models have been set up. The laboratory is run under an open-access model with internal and external users under a research collaboration contract. Website: https://www.helmholtz-hzi.de/broenstrup Email: mark.broenstrup@helmholtz-hzi.de The Edinburgh Cancer Discovery Unit (ECDU) is an academic research group located within the Cancer Research UK Edinburgh Centre, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh in Scotland, United Kingdom.3Warchal S.J. Dawson J.C. Carragher N.O. Evaluation of Machine Learning Classifiers to Predict Compound Mechanism of Action When Transferred across Distinct Cell Lines.SLAS Discov. 2019; 24: 224-233Google Scholar The ECDU was founded in 2011 as a not-for-profit activity to provide a multidisciplinary group of core skills embracing advanced technology platforms and disease models, which drive innovations in oncology drug discovery and development. The ECDU research staff currently comprises Professor Neil Carragher (director), seven senior scientists, and three full-time postgraduate PhD students. Key technologies used within the unit include high-content imaging, confocal and multiphoton confocal imaging, image analysis, reverse-phase protein array, and NanoString (Seattle, WA) molecular profiling of transcriptomic and posttranslation pathway networks. The ECDU mission is to develop and apply novel genetically defined 2D and 3D cell- and tissue-based assays that represent advances over the current state of the art in disease relevance and inform subsequent preclinical and clinical development strategies. The research unit is highly proficient in image-based phenotypic screening using predominantly small-molecule chemical libraries (e.g., approved drugs, annotated chemogenomic probe compounds, and diverse lead-like chemical libraries) and, through partnerships, therapeutic antibodies and peptides. The laboratories are equipped with the latest kinetic (IncuCyte Zoom, Essen BioScience, Sartorius, Göttingen, Germany) and high-content (ImageXpress-microXL, Molecular Devices, LLC, Sunnyvale, CA) screening platforms, fully integrated with plate handling robotics, barcode sample tracking, and bespoke multiparametric image analysis/informatics workflows. The unit also routinely employs both forward-phase and reverse-phase protein microarray platforms (Aushon 2470, GeSim Nanoplotter 2.1E, Radeberg, Germany; Innopsys, Carbonne, France; InnoScan 710 IR and Zeptosens; and the NanoString, Seattle, WA n-counter platform) to profile preclinical and clinical samples and drug mechanism of action at transcriptomic and posttranslational pathway network levels. The ECDU works in close collaboration with several pharmaceutical and biotechnology industry partners and academic research groups to identify hit molecules, advance small-molecule lead generation, and classify compound mechanism of action through multiparametric high-content and pathway profiling. The ECDU provides an open-access model to both internal University of Edinburgh research groups and external academic or industry organizations through either fee-for-service or joint research collaboration agreements. The ECDU operates a full-cost recovery model for projects with external partners and recovery of only consumables for Cancer Research UK-funded groups within the University of Edinburgh. Intellectual property (IP) policy is flexible and dictated on a case-by-case basis dependent upon the nature of the project and research agreement (i.e., distinct IP arrangements are considered for fee-for-service or research collaboration agreements). IP arrangements are pre-agreed and documented in the service or research collaboration agreements prior to commencing work with external partners. All contracts and research agreements are arranged through the business development function at Edinburgh Innovations. Website: https://www.ed.ac.uk/cancer-centre/impact-and-innovation/translational-science/edinburgh-cancer-discovery-unit-ecdu Email: edinburgh.innovations@ed.ac.uk The Technology Development Studio (TDS) is an academic screening facility that was created in 2004 at the Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG) in Dresden, Germany.4Janosch A. Kaffka C. Bickle M. Unbiased Phenotype Detection Using Negative Controls.SLAS Discov. 2019; 24: 234-241Google Scholar The mission of the facility is to provide state-of-the-art cellular screening services for its users and to develop novel technologies where required (hence the name of the facility). The facility specializes in high-throughput microscopy since this technology provides great flexibility and allows in-depth analysis of biological systems. Homogeneous assays such as luminescence or fluorometric measurements and biochemical assays are also run when required. Both genomic and chemical screens can be run, and the facility has several genome-wide RNAi libraries and approximately 130,000 compounds. The TDS has screened a wide diversity of cellular systems ranging from simple immortalized cell lines to primary cells and stem cells both in 2D and 3D. Additionally, the facility has also screened small model organisms such as Caenorhabditis elegans and zebrafish. Protocols have been developed for handling 3D nonadherent objects with standard liquid handlers. Furthermore, optical clearing protocols and methods for imaging 3D objects in 384-well plates have been optimized. Like all facilities at the MPI-CBG, the TDS offers its excess capacity to outside users and has carried out screens for many academic and industrial collaborators not associated with the MPI-CBG. Distribution of intellectual property is decided on case-by-case by the users based on the contribution of each of the parties involved. To provide screening services to outside clients, a full-cost accounting system is used that considers salaries, consumables, instrument time, depreciation, and overheads. The TDS helps prepare grants and participates in funding calls to cover the cost of screening. Services range from designing a screening assay from scratch to executing an already optimized assay and running the analysis of the data on the institute’s computer cluster. The data are owned by the client and transferred at the end of the project. To keep the costs minimal, the TDS uses open-source software for its work. Image analysis is mainly carried out with CellProfiler, Fiji, and sometimes bespoke Python image analysis scripts developed for challenging applications. For data mining, the TDS has developed a suite of software tools in the KNIME software platform. KNIME allows building analytical pipelines in a user-friendly graphical interface that helps to visualize the flow of data. The TDS has developed many tools specific for screening applications, such as plate viewers, normalization nodes, data annotations, and population analysis nodes, which can be downloaded from the KNIME website (https://www.knime.com/downloads/download-knime). One very powerful tool that the TDS introduced to the KNIME platform is scripting nodes for R and Python. These allow users to write their code in those programming languages and, with the insertion of a few lines into the code, to generate a graphical user interface in KNIME using RGG (R GUI Generator). In this manner, a computer scientist can rapidly deploy code to scientists who are not comfortable with programming scripts. Website: http://www.mpi-cbg.de/facilities/profiles/ht-tds.html Email: bickle@mpi-cbg.de The Pharmacy Chemical Biology Center (PCBC) in the University of Pittsburgh (Pitt) School of Pharmacy was founded in 2011, evolving out of a high-throughput screening (HTS) center that was founded in 2005 with resources from the Schools of Medicine, Pharmacy, and Arts and Science.8Close D.A. Wang A.X. Kochanek S.J. et al.Implementation of the NCI-60 Human Tumor Cell Line Panel to Screen 2260 Cancer Drug Combinations to Generate >3 Million Data Points Used to Populate a Large Matrix of Anti-Neoplastic Agent Combinations (ALMANAC) Database.SLAS Discov. 2019; 24: 242-263Google Scholar The Pittsburgh Molecular Library Screening Center (2005–2008) and the Pittsburgh Specialized Application Center (2009–2012) were partly supported by funding from the National Institute of Health’s (NIH) Roadmap Initiative Molecular Library Pilot Screening Center Network and the National Cancer Institute’s (NCI) Chemical Biology Consortium, respectively. The PCBC was created as part of the School of Pharmacy’s D4Janosch A. Kaffka C. Bickle M. Unbiased Phenotype Detection Using Negative Controls.SLAS Discov. 2019; 24: 234-241Google Scholar initiative to provide one-stop access to drug discovery, development, and delivery expertise in an interactive and collaborative environment. Research faculty in the D4Janosch A. Kaffka C. Bickle M. Unbiased Phenotype Detection Using Negative Controls.SLAS Discov. 2019; 24: 234-241Google Scholar team have a proven track record in drug discovery and preclinical drug development in both the pharmaceutical and academic sectors. The faculty’s complementary and overlapping capabilities encompass the drug discovery and development process and address the major causes of drug failure. Dr. Paul A. Johnston is the principal investigator (PI) of the PCBC and has 28 years of drug discovery experience in the pharmaceutical, biotechnology, and academic sectors. The PCBC is staffed by three full-time research scientists and varying numbers of graduate students or visiting scientists, most recently two PhD students, one MS student, and one visiting postdoc. The Molecular Devices SpectraMax M5e and Envision (PerkinElmer, Waltham, MA) microtiter plate reader platforms provide multimode assay detection capabilities for UV/Vis absorbance, fluorescence intensity, fluorescence polarization, time-resolved fluorescence resonance energy transfer (TR-FRET), homogenous time-resolved fluorescence (HTRF), and luminescence. The Molecular Devices (Sunnyvale, CA) ImageXpress Micro field-based automated high-content screening (HCS) imaging platform, MetaXpress Imaging and Analysis software, and MDCStore database allow for the capture, analysis, and storage of images acquired in transmitted light and/or five fluorescent channels. The PCBC uses the ScreenAble laboratory information management system software to process and analyze compound information and HTS/HCS data. The PCBC has a 10,000-compound nonpeptide peptido-mimetic diversity subset of a 142,000 protein–protein interaction library, and a 50,000-compound diversity library selected from a 410,000 core library, which enables it to effectively sample a compound diversity of 635,500 compounds. The PCBC provides guidance in assay format selection and assistance with assay development, optimization, and implementation of target-based biochemical and cell-based HTS assays, HCS imaging assays, and phenotypic drug discovery screens. The PCBC performs active confirmation, counterscreens in orthogonal assay formats, hit characterization in secondary and tertiary assays, mechanism of action studies, and bioassay support for medicinal chemistry lead optimization efforts. Projects can be loaded into the PCBC portfolio at any of these stages and are supported through a variety of funding sources, including NIH grants awarded to the PI or his collaborators at Pitt or other academic institutions (national and international), donations from philanthropic foundations, and research contracts with other academic institutions and biotechnology or pharmaceutical companies. Project budgets include personnel salaries and benefits, reagents, consumables, and Pitt institutional indirect costs. Depending upon the funding source, any unassigned intellectual property rights are subject to negotiation with the Pitt office of research. Website: http://www.pharmacy.pitt.edu/directory/profile.php?profile=856 Email: paj18@pitt.edu The Stem Cell Hotel is an innovative collaborative phenotyping unit located within the Centre for Stem Cells and Regenerative Medicine (CSCRM) at King’s College London, United Kingdom.10Wiseman E. Zamuner A. Tang Z. et al.Integrated Multiparametric High-Content Profiling of Endothelial Cells.SLAS Discov. 2019; 24: 264-273Google Scholar It is based at the 28th Floor of Guy’s Tower, Great Maze Pond, with spectacular views over the Thames and the city. The center was inaugurated in December 2015 and the Stem Cell Hotel started its operation. A dedicated team of stem cell scientists, imaging experts, and analysts, with help from interns, bioinformaticians, and business advisors, is forming around the project, spearheaded by Dr. Davide Danovi. Technologies from several providers enable microscopy and high-content analysis, cell-based assays, and data integration. The Stem Cell Hotel offers access to high-content imaging (PerkinElmer Operetta and Operetta CLS, PerkinElmer, Waltham, MA; NanoEntek, Julistage, Guro-gu, Seoul, Korea; and Essen BioScience IncuCyte Zoom, Sartorius, Gottingen, Germany) and quantitative phase imaging (Livecyte, Phasefocus, Sheffield, UK) devices. Resources and expertise in the areas of stem cell biology, artificial microenvironments for cell culture, and high-content imaging are provided as services. This includes assistance for assay development, image acquisition, and dedicated data analysis and integration. The Stem Cell Hotel develops robust methods for profiling and benchmarking cells for cell therapy and drug discovery applications. It uses dynamic and endpoint imaging and high-content analysis integrated with genomics and other biological datasets. The operation also leverages expertise from a critical mass of scientists and innovative research projects currently ongoing at the center, such as the development of standard methods for characterization of induced pluripotent stem cells (iPSCs). Created within the framework of the Human Induced Pluripotent Stem Cell Initiative (HIPSCI) and serving the UK Regenerative Medicine Platform (UKRMP), the facility offers external users services ranging from initial training on the instruments to more in-depth assistance in assay development, acquisition, and further data analysis. Its cost model varies from pure charging for the time of use of instruments and consumables to scientific collaborations, from co-development of software and applications with technology providers to contract research-type projects. Importantly, the facility works effectively with technology providers embedding instruments and technologies in the space. This has taken the form of leases, extended demos, beta testing of software, and agreements to offer the possibility to showcase devices to future potential customers. These innovative options foster a constructive dialogue and offer a testing bed for research and industry to understand needs and mature products and solutions. As an example, one of the center’s technology providers can establish a strategic partnership to provide in-house technical support with the use of the entire set of instruments, ranging from assay development to image analysis. The Stem Cell Hotel’s policy sees intellectual property (IP) staying with the user unless otherwise discussed on specific projects that require significant input from the Stem Cell Hotel. Born from research, boldly translational, and embracing the spirit of open innovation, the SCH grants access to state-of-the-art technology and serves communities centered around academic, clinical, and commercial research in a highly collaborative environment. Website: http://www.kclstemcellhotel.org Email: davide.danovi@kcl.ac.uk The CellNetworks Advanced Biological Screening Core Facility was established in 2007 as one of the first CellNetworks Core Facilities and is located at Heidelberg University in the BioQuant Center for “Quantitative Analysis of Molecular and Cellular Biosystems” in Heidelberg, Germany.5Starkuviene V. Kallenberger S.M. Beil N. et al.High-Density Cell Arrays for Genome-Scale Phenotypic Screening.SLAS Discov. 2019; 24: 274-283Google Scholar The facility is equipped with state-of-the art instruments, and its experts possess long-term experience in the field of biologicals, RNAi screening, automated screening microscopy, and data analysis, and lately, CRISPR-mediated gene editing. The facility offers support in assay development, automated sample preparation, and high-throughput solid-phase-based transfection in multiwell plates or cell microarrays. A number of focused and genome-wide libraries of siRNAs, microRNAs, cDNAs, and crRNAs are available. In addition, the facility facilitates the contact between customers and experts on the campus to help establish collaborations and strengthen the research network in the field of biological screening in Heidelberg. In this manner, pilot projects starting out as services within the facility are developed into successful multilateral collaborations. The facility has either been a partner with or played a leading role in several projects funded by the European Union, German Federal Ministry of Education and Research (BMBF), and Baden Württemberg Stiftung. Recently, the High-Content Analysis of the Cell (HiCell) group was established with the aim to design, develop, and apply novel technologies for high-content screening and analysis. Once tested and standardized, the novel technologies are incorporated into the portfolio of the Advanced Biological Screening Facility and become accessible for users. HiCell focuses on the development of methodologies to interfere with cell function on DNA, mRNA, and protein levels, on the miniaturization of cellular assays such as the cell microarrays presented in this issue,5Starkuviene V. Kallenberger S.M. Beil N. et al.High-Density Cell Arrays for Genome-Scale Phenotypic Screening.SLAS Discov. 2019; 24: 274-283Google Scholar and on combinatorial assays. The facility also offers correlative microscopy combining high-speed and super-resolution imaging as well as 3D assays and imaging. Lately, it has been focusing on single-cell analysis. Websites: Advanced Biological Screening Facility: http://www.bioquant.uni-heidelberg.de/index.php?id=42 High-Content Analysis of the Cell (HiCell): http://www.bioquant.uni-heidelberg.de/research/groups/high-content-analysis-of-the-cell-hicell.html Email: holger.erfle@bioquant.uni-heidelberg.de The Drug Discovery Initiative at the University of Tokyo, Japan, aims to promote academic research and innovation in drug discovery. It supports academic and industrial researchers who want to screen chemical samples to find either chemical biological tools, drug leads, or agrochemicals.6Imamura R.M. Kumagai K. Nakano H. et al.Inexpensive High-Throughput Screening of Kinase Inhibitors Using One-Step Enzyme-Coupled Fluorescence Assay for ADP Detection.SLAS Discov. 2019; 24: 284-294Google Scholar The Drug Discovery Initiative has constructed a chemical library consisting of about 280,000 samples chosen primarily on druggability and structural diversity. The collection includes 63,000 samples deposited by industry since 2006. These chemicals are provided (in assay-ready plates if required) to researchers in Japan who are willing to disclose their research goals and report their assay results to the initiative under a confidentiality agreement. The users are required to pay the consumables and shipping costs, while the chemical samples themselves are free of charge. The initiative does not claim any rights to the results of the screens in the absence of intellectual contribution. The initiative has provided more than 22 million samples to more than 500 users so far. The initiative has various screening instruments that are available to users. Consul