Structural Genomics Consortium

The Structural Genomics Consortium (SGC) is a public-private-partnership focusing on elucidating the functions and disease relevance of all proteins encoded by the human genome, with an emphasis on those that are relatively understudied.[1][2][3] The SGC places all its research output into the public domain without restriction and does not file for patents and continues to promote open science.[4][5][6][7][8][9][10][11][12][13][14] Two recent publications revisit the case for open science.[15][16] Founded in 2003, and modelled after the Single Nucleotide Polymorphism Database (dbSNP) Consortium, the SGC is a charitable company whose Members comprise organizations that contribute over $5,4M Euros to the SGC over a five-year period. The Board has one representative from each Member and an independent Chair, who serves one 5-year term. The current Chair is Anke Müller-Fahrnow (Germany), and previous Chairs have been Michael Morgan (U.K.), Wayne Hendrickson (U.S.A.), Markus Gruetter (Switzerland) and Tetsuyuki Maruyama (Japan). The founding and current CEO is Aled Edwards (Canada). The founding Members of the SGC Company were the Canadian Institutes of Health Research, Genome Canada, the Ontario Research Fund, GlaxoSmithKline and Wellcome Trust. The current (March 2022) Members comprise Bayer Pharma AG, Bristol Myers Squibb, Boehringer Ingelheim, the Eshelman Institute for Innovation, Genentech, Genome Canada, Janssen, Merck KGaA, Pfizer, and Takeda.

SGC research activities take place in a coordinated network of university-affiliated laboratories – at Goethe University Frankfurt, Karolinska Institutet, McGill University, and the Universities of North Carolina at Chapel Hill and Toronto. The research activities are supported both by funds from the SGC Company as well as by grants secured by the scientists affiliated with the SGC programs. At each university, the scientific teams are led by a Chief Scientist, who are Stefan Knapp (Goethe University Frankfurt), Michael Sundstrom (Karolinska Institutet), Ted Fon (McGill University), Tim Willson (University of North Carolina at Chapel Hill), and Cheryl Arrowsmith (University of Toronto). The SGC currently comprises ~200 scientists.

Notable achievements

Chemical biology of human proteins

Structural biology of human proteins – The SGC has so far contributed over 2000 protein structures of human proteins of potential relevance for drug discovery into the public domain since 2003.[17] Structures that constitute complexes with synthetic small molecules is aided by a partnership with the Diamond synchrotron in Oxfordshire.[18] The chemical probe program prioritizes (members of) protein families that are relatively understudied, or which may be currently relevant to human biology and drug discovery. These families include epigenetic signaling,[19][20] solute transport,[21][22] protein proteostasis,[23][24][25][26][27] and protein phosphorylation.[12][28][29] The protein family approach is supported by publicly available bioinformatics tools (ChromoHub,[30] UbiHub[31]), family-based protein production and biochemistry, crystallography and structure determination, biophysics, and cell biology (for example target engagement assays). The SGC has (so far) contributed ~120 chemical probes[10][32][33] into the public domain over the past decade, and >25,000 samples of these probes have been distributed to the scientific community. The chemical probes conform to the now community-standard quality criteria created by the SGC and its collaborative network.[10][34][35][36][37][38]

  1. Epigenetic chemical probes that have generated clinical interest in their targets include PFI-1[39] and JQ1[40] for the BET family, UNC0642[41] for G9a/GLP, UNC1999[42] for EZH2/H1, LLY-283[43] and GSK591[44] for PRMT5, and OICR-9429[45] for WDR5. The WDR5 chemical probe was optimized (by a company external to the SGC) for clinical amenability and is the subject of investment from Celgene.
  2. Kinases have seen 50 drugs approved by the FDA for treatment of cancer, inflammation, and fibrosis.[46] A review[47] from two and a half years ago, a recent preprint,[48] and peer-reviewed publication[49] highlight low coverage of kinases both by peer-reviewed publications and 3D structures. In the last 4 years laboratories in Frankfurt, North Carolina and Oxford have developed chemical matter to help biologists study underrepresented kinases. In collaboration with pharmaceutical companies and academia, 15 chemical probes, and version 1.0 of 187 chemogenomic inhibitors (aka KCGS) for 215 kinases[12][29] have been co-developed.
  3. Integral membrane proteins are permanently attached to the cell membrane. The family includes the solute carrier (SLC) proteins. The SLCs are largely unexplored therapeutically ~30% are considered ‘orphaned’ because their substrate specificity and biological function are unknown. In 2019 a public-private partnership comprising 13 partners, including the SGC, formed The RESOLUTE Consortium[22] with funding from the IMI. RESOLUTE’s goal is to encourage research on SLCs .
  4. The Target Enabling Package (TEP) is a collection reagents and knowledge on a protein target aimed to catalyze biochemical and chemical exploration, and characterization of proteins with genetic linkage to key disease areas. The SGC has opened target nominations to the public.[50]
  5. The Unrestricted Leveraging of Targets for Research Advancement and Drug Discovery (ULTRA-DD) program, funded by the European Commission’s Innovative Medicines Initiative (IMI), aims to identify and validate under-explored targets in auto-immune and inflammatory disease models. Patient-derived cell lines are screened against chemical modulators (including chemical probes and chemogenomic compounds) with the intention of obtaining phenotypic read-outs in a disease relevant context.[51]
  6. The Enabling and Unlocking biology in the Open (EUbOPEN) program, funded by the IMI, aims to assemble a chemogenomic library for ~1,000 proteins, discover ~100 high-quality, chemical probes, establish infrastructure to characterize these compounds, disseminate robust protocols for primary patient cell-based assays, while establishing the infrastructure to seed a global effort on addressing the entire druggable genome.

Non-human proteins

The Structure-guided Drug Discovery Coalition (SDDC) comprises the Seattle Structural Genomics Center for Infectious Disease (SSGCID), the Midwest Center for Structural Genomics, the Center for Structural Genomics of Infectious Diseases (CSGID), and drug discovery teams from academia and industry has resulted in 7 early drug leads for tuberculosis (TB), malaria, and cryptosporidiosis. The SDDC receives funding from participating academic initiatives and the Bill & Melinda Gates Foundation.

The University of North Carolina at Chapel Hill and the Eshelman Institute for Innovation, launched Rapidly Emerging Antiviral Drug Development Initiative (READDI™) and Viral Interruption to Medicines Initiative (VIMI™). REDDI™ is modelled after the non-profit drug research and development Drugs for Neglected Diseases Initiative (DNDi). READDI™ and VIMI™ are non-profit, open science initiatives that focus on developing therapeutics for all pandemic-capable viruses.[52]

Open Science

Open science is a key operating principle.[53] A Trust Agreement[4][5][6][54] is signed before reagents are shared with researchers. These reagents include cDNA clones (Addgene), chemical probes,[55] and 3D structures.[17] Tools to promote open science include open lab notebooks.[9] The latter platform is being used to share research on (for example) Diffuse intrinsic pontine glioma (DIPG), Fibrodysplasia ossificans progressiva, Huntington’s disease,[8][56] Parkinson’s disease, and Chordoma.

Open Drug Discovery

The for-profit spin-off companies M4K Pharma (Medicines for Kids), M4ND Pharma (Medicines for Neurological Diseases) and M4ID Pharma (Medicines for Infectious Diseases) do not file patents and practise open science. The M4 companies are wholly owned by a Canadian charity Agora Open Science Trust whose mandate is to share scientific knowledge and ensure affordable access to all medicines. M4K Pharma has the most advanced open drug discovery program[14] and is supported with funding from the Ontario Institute for Cancer Research, The Brain Tumour Charity, Charles River Laboratories and Reaction Biology, and with contributions from scientists at the Universities of McGill, North Carolina, Oxford, Pennsylvania, and Toronto and in the Sant Joan de Déu hospital, the University Health Network hospitals, the Hospital for Sick Children, and The Institute for Cancer Research. M4K Pharma is developing a selective inhibitor of ALK2 for DIPG, a uniformly fatal pediatric brain tumour.[14]

History

The Concept

In 2000, a group of companies and Wellcome conceptualized forming a Structural Genomics Consortium to focus on determining the three-dimensional structures of human proteins.[1] The consortium must place all structural information and supporting reagents into the public domain without restriction. This effort was designed to complement other structural genomics programs in the world.

Phase I (2004-2007)

The SGC scientific program was launched, with activities at the Universities of Oxford and Toronto, and with a mandate to contribute >350 human protein structures into the public domain. To be counted toward these goals, the proteins had to derive from a pre-defined list and the protein structures were required to meet pre-defined quality criteria. The quality of protein structures was and continues to be adjudicated by a committee of independent academic scientists. Michael Morgan was the Chair of the SGC Board, and the scientific activities were led by Cheryl Arrowsmith (Toronto) and Michael Sundstrom (Oxford). In mid 2005, VINNOVA, the Knut and Alice Wallenberg Foundation and the Foundation for Strategic Research (SSF) established the Swedish research node of the SGC. Experimental activities started at the Karolinska Institutet in Stockholm, led by Pär Nordlund and Johan Weigelt. Together, the three SGC laboratories contributed 392 human protein structures into the public domain. A pilot program in the structural biology of proteins in the malaria parasite was also initiated.[57]

Phase II (2007-2011)

The new goal for structures was 650. The SGC focused considerable activities in the areas of ubiquitination, protein phosphorylation, small G-proteins and epigenetics, and also initiated an effort in the structural biology of integral membrane proteins. In this phase, the SGC determined the structures of 665 human proteins from its Target List. With support from Wellcome and GSK, the SGC launched a program to develop freely-available chemical probes to proteins involved in epigenetic signalling which at the time were under studied.[2][5] The quality of each chemical probe was subject to two levels of review prior to their dissemination to the public. The first was internal, through a Joint Management Committee comprising representatives from each member organization. The second was provided by a group of independent experts selected from academia. This level of oversight is aimed at developing reagents that support reproducible research.[58][59][13] It ultimately led to the creation of the Chemical Probes Portal. The SGC Memberships expanded to include Merck, Sharpe and Dohme, and Novartis. Wayne Hendrickson served as the Chair of the SGC Board.

Phase III (2011-2015)

The SGC mandate diversified to include 200 human proteins including 5 integral membrane proteins and chemical probes (30). Many of the chemical probes’ programs were undertaken in partnership with scientists in the pharmaceutical companies, which made the commitment to contribute the collaborative chemical probe into the public domain, without restriction. In Phase III, the SGC, along with the SSGCID (https://www.ssgcid.org/) and the CSGID (https://csgid.org/) launched the SDDC. SGC Memberships: AbbVie, Bayer AG, Boehringer Ingelheim, Eli Lilly and Janssen. Merck, Sharpe and Dohme and the Canadian Institutes for Health Research left the consortium. Markus Gruetter became the Chair of the SGC Board.[60]

Phase IV (2015-2020)

This phase built on the goals of previous phases but included well-characterized antibodies to human proteins. The SGC initiated a concerted effort to develop disease-relevant, cell-based assays using (primary) cells or tissue from patients. This phase saw the launch of research activities at Goethe University in Frankfurt, at McGill University, and at the Universities of Campinas and North Carolina, and participation in ULTRADD and RESOLUTE[21][22] within IMI. SGC Memberships: Merck KGaA, the Eshelman Institute for Innovation, Merck, Sharpe and Dohme joined while GSK and Eli Lilly left. Tetsuyuki Maruyama became the Chair of the Board.

The Future - Target 2035

Target 2035 is an open science movement with the goal of creating chemical[12][24][29][32][33] and/or biological[13][59] tools for the entire proteome by 2035.[61] The launch in November 2020 and monthly webinars have and continue to be free to attend. Supporting projects currently underway include the SGC’s epigenetics chemical probe program,[62][63][64] the NIH’s Illuminating the Druggable Genome initiative for under-explored kinases, GPCR’s and ion channels,[65][66][67] IMI’s RESOLUTE project on human SLCs,[22] and IMI's Enabling and Unlocking Biology in the Open (EUbOPEN). These teams are linked to SGC’s global collaborative network.[2][10][35][51][68][13][59]

Selected publications

Chemogenomics, protein degradation
  • Carter, AJ; Kraemer, O; Zwick, M; Mueller-Farhnow, A; Arrowsmith, CH; Edwards, AM (November 2019). "Target 2035: probing the human proteome". Drug Discovery Today. 24 (11): 2111–2115. doi:10.1016/j.drudis.2019.06.020. PMID 31278990.
  • Wells, CI (2021). "The Kinase Chemogenomic Set (KCGS): An Open Science Resource for Kinase Vulnerability Identification". International Journal of Molecular Sciences. 22 (2): 566. doi:10.3390/ijms22020566. PMC 7826789. PMID 33429995.
  • Schapira, M; Calabrese, MF; Bullock, AN; Crews, CM (December 2019). "Targeted protein degradation: expanding the toolbox". Nature Reviews Drug Discovery. 18 (12): 949–963. doi:10.1038/s41573-019-0047-y. PMID 31666732. S2CID 204942300.
  • Superti-Furga, G; et, al. (July 2020). "The RESOLUTE consortium: unlocking SLC transporters for drug discovery". Nature Reviews Drug Discovery. 19 (7): 429–430. doi:10.1038/d41573-020-00056-6. PMID 32265506. S2CID 215406274.

Patient-derived cell assays

Open science

Reproducibility

References
  1. Williamson, AR (2000). "Creating a structural genomics consortium". Nature Structural Biology. 7: 953. doi:10.1038/80726. PMID 11103997. S2CID 35185565.
  2. Edwards, AM; et, al. (2011). "Too many roads not taken". Nature. 470 (2333): 163–165. arXiv:1102.0448. Bibcode:2011Natur.470..163E. doi:10.1038/470163a. PMID 21307913. S2CID 4429387.
  3. Davis, Andrew M.; Engkvist, Ola; Fairclough, Rebecca J.; Feierberg, Isabella; Freeman, Adrian; Iyer, Preeti (2021-02-13). "Public-Private Partnerships: Compound and Data Sharing in Drug Discovery and Development". SLAS Discovery. 26 (5): 604–619. doi:10.1177/2472555220982268. ISSN 2472-5552. PMID 33586501. S2CID 231928371.
  4. Edwards, Aled (September 2008). "Open-source science to enable drug discovery". Drug Discovery Today. 13 (17–18): 731–733. doi:10.1016/j.drudis.2008.04.011. ISSN 1359-6446. PMID 18790412.
  5. Edwards, Aled M.; Bountra, Chas; Kerr, David J.; Willson, Timothy M. (July 2009). "Open access chemical and clinical probes to support drug discovery". Nature Chemical Biology. 5 (7): 436–440. doi:10.1038/nchembio0709-436. ISSN 1552-4469. PMID 19536100.
  6. Masum, Hassan; Rao, Aarthi; Good, Benjamin M.; Todd, Matthew H.; Edwards, Aled M.; Chan, Leslie; Bunin, Barry A.; Su, Andrew I.; Thomas, Zakir; Bourne, Philip E. (2013). "Ten simple rules for cultivating open science and collaborative R&D". PLOS Computational Biology. 9 (9): e1003244. Bibcode:2013PLSCB...9E3244M. doi:10.1371/journal.pcbi.1003244. ISSN 1553-7358. PMC 3784487. PMID 24086123.
  7. Morgan, Maxwell Robert; Roberts, Owen Gwilym; Edwards, Aled Morgan (2018). "Ideation and implementation of an open science drug discovery business model - M4K Pharma". Wellcome Open Research. 3: 154. doi:10.12688/wellcomeopenres.14947.1. ISSN 2398-502X. PMC 6346698. PMID 30705971.
  8. Harding, Rachel J. (January 2019). "Open notebook science can maximize impact for rare disease projects". PLOS Biology. 17 (1): e3000120. doi:10.1371/journal.pbio.3000120. ISSN 1545-7885. PMC 6366684. PMID 30689629.
  9. Schapira, Matthieu; Harding, Rachel J. (2019-04-02). "Open laboratory notebooks: good for science, good for society, good for scientists". F1000Research. 8: 87. doi:10.12688/f1000research.17710.2. ISSN 2046-1402. PMC 6694453. PMID 31448096.
  10. Müller, Susanne; Ackloo, Suzanne; Arrowsmith, Cheryl H.; Bauser, Marcus; Baryza, Jeremy L.; Blagg, Julian; Böttcher, Jark; Bountra, Chas; Brown, Peter J.; Bunnage, Mark E.; Carter, Adrian J. (20 April 2018). "Donated chemical probes for open science". eLife. 7. doi:10.7554/eLife.34311. ISSN 2050-084X. PMC 5910019. PMID 29676732.
  11. Drewry, David H.; Wells, Carrow I.; Zuercher, William J.; Willson, Timothy M. (June 2019). "A Perspective on Extreme Open Science: Companies Sharing Compounds without Restriction". SLAS Discovery. 24 (5): 505–514. doi:10.1177/2472555219838210. ISSN 2472-5560. PMC 6624833. PMID 31034310.
  12. Wells, Carrow I.; Al-Ali, Hassan; Andrews, David M.; Asquith, Christopher R. M.; Axtman, Alison D.; Dikic, Ivan; Ebner, Daniel; Ettmayer, Peter; Fischer, Christian; Frederiksen, Mathias; Futrell, Robert E. (2021-01-08). "The Kinase Chemogenomic Set (KCGS): An Open Science Resource for Kinase Vulnerability Identification". International Journal of Molecular Sciences. 22 (2): 566. doi:10.3390/ijms22020566. ISSN 1422-0067. PMC 7826789. PMID 33429995.
  13. Laflamme, Carl; McKeever, Paul M.; Kumar, Rahul; Schwartz, Julie; Kolahdouzan, Mahshad; Chen, Carol X.; You, Zhipeng; Benaliouad, Faiza; Gileadi, Opher; McBride, Heidi M.; Durcan, Thomas M. (15 October 2019). "Implementation of an antibody characterization procedure and application to the major ALS/FTD disease gene C9ORF72". eLife. 8. doi:10.7554/eLife.48363. ISSN 2050-084X. PMC 6794092. PMID 31612854.
  14. Ensan, Deeba; Smil, David; Zepeda-Velázquez, Carlos A.; Panagopoulos, Dimitrios; Wong, Jong Fu; Williams, Eleanor P.; Adamson, Roslin; Bullock, Alex N.; Kiyota, Taira; Aman, Ahmed; Roberts, Owen G. (2020-05-14). "Targeting ALK2: An Open Science Approach to Developing Therapeutics for the Treatment of Diffuse Intrinsic Pontine Glioma". Journal of Medicinal Chemistry. 63 (9): 4978–4996. doi:10.1021/acs.jmedchem.0c00395. ISSN 1520-4804. PMC 8213057. PMID 32369358.
  15. Gold, E. Richard (June 2021). "The fall of the innovation empire and its possible rise through open science". Research Policy. 50 (5): 104226. doi:10.1016/j.respol.2021.104226. PMC 8024784. PMID 34083844.
  16. Jones, Molly Morgan; Chataway, Joanna (2021-03-04). "The Structural Genomics Consortium: successful organisational technology experiment or new institutional infrastructure for health research?". Technology Analysis & Strategic Management. 33 (3): 296–306. doi:10.1080/09537325.2021.1882673. ISSN 0953-7325. S2CID 232245414.
  17. "Structure Gallery". SGC. Retrieved 2020-09-09.
  18. Collins, Patrick M.; Douangamath, Alice; Talon, Romain; Dias, Alexandre; Brandao-Neto, Jose; Krojer, Tobias; von Delft, Frank (2018). Achieving a Good Crystal System for Crystallographic X-Ray Fragment Screening. Methods in Enzymology. Vol. 610. pp. 251–264. doi:10.1016/bs.mie.2018.09.027. ISBN 9780128153833. ISSN 1557-7988. PMID 30390801.
  19. Arrowsmith, Cheryl H.; Bountra, Chas; Fish, Paul V.; Lee, Kevin; Schapira, Matthieu (2012-04-13). "Epigenetic protein families: a new frontier for drug discovery". Nature Reviews. Drug Discovery. 11 (5): 384–400. doi:10.1038/nrd3674. ISSN 1474-1784. PMID 22498752. S2CID 5478921.
  20. Huston, Andrea; Arrowsmith, Cheryl H.; Knapp, Stefan; Schapira, Matthieu (August 2015). "Probing the epigenome". Nature Chemical Biology. 11 (8): 542–545. doi:10.1038/nchembio.1871. ISSN 1552-4469. PMID 26196765.
  21. César-Razquin, Adrián; Snijder, Berend; Frappier-Brinton, Tristan; Isserlin, Ruth; Gyimesi, Gergely; Bai, Xiaoyun; Reithmeier, Reinhart A.; Hepworth, David; Hediger, Matthias A.; Edwards, Aled M.; Superti-Furga, Giulio (2015-07-30). "A Call for Systematic Research on Solute Carriers". Cell. 162 (3): 478–487. doi:10.1016/j.cell.2015.07.022. ISSN 1097-4172. PMID 26232220. S2CID 15427088.
  22. Superti-Furga, Giulio; Lackner, Daniel; Wiedmer, Tabea; Ingles-Prieto, Alvaro; Barbosa, Barbara; Girardi, Enrico; Goldmann, Ulrich; Gürtl, Bettina; Klavins, Kristaps; Klimek, Christoph; Lindinger, Sabrina (July 2020). "The RESOLUTE consortium: unlocking SLC transporters for drug discovery". Nature Reviews. Drug Discovery. 19 (7): 429–430. doi:10.1038/d41573-020-00056-6. ISSN 1474-1784. PMID 32265506. S2CID 215406274.
  23. Liu, Lihua; Damerell, David R.; Koukouflis, Leonidas; Tong, Yufeng; Marsden, Brian D.; Schapira, Matthieu (15 August 2019). "UbiHub: a data hub for the explorers of ubiquitination pathways". Bioinformatics. 35 (16): 2882–2884. doi:10.1093/bioinformatics/bty1067. ISSN 1367-4811. PMC 6691330. PMID 30601939.
  24. Schapira, Matthieu; Calabrese, Matthew F.; Bullock, Alex N.; Crews, Craig M. (December 2019). "Targeted protein degradation: expanding the toolbox". Nature Reviews. Drug Discovery. 18 (12): 949–963. doi:10.1038/s41573-019-0047-y. ISSN 1474-1784. PMID 31666732. S2CID 204942300.
  25. Harding, Rachel J.; Ferreira de Freitas, Renato; Collins, Patrick; Franzoni, Ivan; Ravichandran, Mani; Ouyang, Hui; Juarez-Ornelas, Kevin A.; Lautens, Mark; Schapira, Matthieu; von Delft, Frank; Santhakumar, Vjayaratnam (9 November 2017). "Small Molecule Antagonists of the Interaction between the Histone Deacetylase 6 Zinc-Finger Domain and Ubiquitin". Journal of Medicinal Chemistry. 60 (21): 9090–9096. doi:10.1021/acs.jmedchem.7b00933. ISSN 1520-4804. PMID 29019676.
  26. Ferreira de Freitas, Renato; Harding, Rachel J.; Franzoni, Ivan; Ravichandran, Mani; Mann, Mandeep K.; Ouyang, Hui; Lautens, Mark; Santhakumar, Vijayaratnam; Arrowsmith, Cheryl H.; Schapira, Matthieu (24 May 2018). "Identification and Structure-Activity Relationship of HDAC6 Zinc-Finger Ubiquitin Binding Domain Inhibitors". Journal of Medicinal Chemistry. 61 (10): 4517–4527. doi:10.1021/acs.jmedchem.8b00258. ISSN 1520-4804. PMID 29741882.
  27. Mann, Mandeep K.; Franzoni, Ivan; de Freitas, Renato Ferreira; Tempel, Wolfram; Houliston, Scott; Smith, Leanna; Vedadi, Masoud; Arrowsmith, Cheryl H.; Harding, Rachel J.; Schapira, Matthieu (27 November 2019). "Discovery of Small Molecule Antagonists of the USP5 Zinc Finger Ubiquitin-Binding Domain" (PDF). Journal of Medicinal Chemistry. 62 (22): 10144–10155. doi:10.1021/acs.jmedchem.9b00988. ISSN 1520-4804. PMID 31663737. S2CID 204975079.
  28. Knapp, Stefan; Arruda, Paulo; Blagg, Julian; Burley, Stephen; Drewry, David H.; Edwards, Aled; Fabbro, Doriano; Gillespie, Paul; Gray, Nathanael S.; Kuster, Bernhard; Lackey, Karen E. (January 2013). "A public-private partnership to unlock the untargeted kinome". Nature Chemical Biology. 9 (1): 3–6. doi:10.1038/nchembio.1113. ISSN 1552-4469. PMID 23238671.
  29. Drewry, David H.; Wells, Carrow I.; Andrews, David M.; Angell, Richard; Al-Ali, Hassan; Axtman, Alison D.; Capuzzi, Stephen J.; Elkins, Jonathan M.; Ettmayer, Peter; Frederiksen, Mathias; Gileadi, Opher (2017). "Progress towards a public chemogenomic set for protein kinases and a call for contributions". PLOS ONE. 12 (8): e0181585. Bibcode:2017PLoSO..1281585D. doi:10.1371/journal.pone.0181585. ISSN 1932-6203. PMC 5540273. PMID 28767711.
  30. "ChromoHub". chromohub.thesgc.org. Retrieved 2020-09-09.
  31. "UbiHub". ubihub.thesgc.org. Retrieved 2020-09-09.
  32. Wu, Qin; Heidenreich, David; Zhou, Stanley; Ackloo, Suzanne; Krämer, Andreas; Nakka, Kiran; Lima-Fernandes, Evelyne; Deblois, Genevieve; Duan, Shili; Vellanki, Ravi N.; Li, Fengling (23 April 2019). "A chemical toolbox for the study of bromodomains and epigenetic signaling". Nature Communications. 10 (1): 1915. Bibcode:2019NatCo..10.1915W. doi:10.1038/s41467-019-09672-2. ISSN 2041-1723. PMC 6478789. PMID 31015424.
  33. Scheer, Sebastian; Ackloo, Suzanne; Medina, Tiago S.; Schapira, Matthieu; Li, Fengling; Ward, Jennifer A.; Lewis, Andrew M.; Northrop, Jeffrey P.; Richardson, Paul L.; Kaniskan, H. Ümit; Shen, Yudao (3 January 2019). "A chemical biology toolbox to study protein methyltransferases and epigenetic signaling". Nature Communications. 10 (1): 19. Bibcode:2019NatCo..10...19S. doi:10.1038/s41467-018-07905-4. ISSN 2041-1723. PMC 6318333. PMID 30604761.
  34. Frye, Stephen V. (March 2010). "The art of the chemical probe". Nature Chemical Biology. 6 (3): 159–161. doi:10.1038/nchembio.296. ISSN 1552-4469. PMID 20154659.
  35. Arrowsmith, Cheryl H.; Audia, James E.; Austin, Christopher; Baell, Jonathan; Bennett, Jonathan; Blagg, Julian; Bountra, Chas; Brennan, Paul E.; Brown, Peter J.; Bunnage, Mark E.; Buser-Doepner, Carolyn (August 2015). "The promise and peril of chemical probes". Nature Chemical Biology. 11 (8): 536–541. doi:10.1038/nchembio.1867. ISSN 1552-4469. PMC 4706458. PMID 26196764.
  36. Blagg, Julian; Workman, Paul (14 August 2017). "Choose and Use Your Chemical Probe Wisely to Explore Cancer Biology". Cancer Cell. 32 (2): 268–270. doi:10.1016/j.ccell.2017.07.010. ISSN 1878-3686. PMC 5559281. PMID 28810148.
  37. Antolin, Albert A.; Tym, Joseph E.; Komianou, Angeliki; Collins, Ian; Workman, Paul; Al-Lazikani, Bissan (15 February 2018). "Objective, Quantitative, Data-Driven Assessment of Chemical Probes". Cell Chemical Biology. 25 (2): 194–205.e5. doi:10.1016/j.chembiol.2017.11.004. ISSN 2451-9448. PMC 5814752. PMID 29249694.
  38. Antolin, Albert A.; Workman, Paul; Al-Lazikani, Bissan (2019-11-28). "Public resources for chemical probes: the journey so far and the road ahead". Future Medicinal Chemistry. 13 (8): 731–747. doi:10.4155/fmc-2019-0231. ISSN 1756-8927. PMID 31778323.
  39. Picaud, Sarah; Da Costa, David; Thanasopoulou, Angeliki; Filippakopoulos, Panagis; Fish, Paul V.; Philpott, Martin; Fedorov, Oleg; Brennan, Paul; Bunnage, Mark E.; Owen, Dafydd R.; Bradner, James E. (2013-06-01). "PFI-1, a highly selective protein interaction inhibitor, targeting BET Bromodomains". Cancer Research. 73 (11): 3336–3346. doi:10.1158/0008-5472.CAN-12-3292. ISSN 1538-7445. PMC 3673830. PMID 23576556.
  40. Filippakopoulos, Panagis; Qi, Jun; Picaud, Sarah; Shen, Yao; Smith, William B.; Fedorov, Oleg; Morse, Elizabeth M.; Keates, Tracey; Hickman, Tyler T.; Felletar, Ildiko; Philpott, Martin (2010-12-23). "Selective inhibition of BET bromodomains". Nature. 468 (7327): 1067–1073. Bibcode:2010Natur.468.1067F. doi:10.1038/nature09504. ISSN 1476-4687. PMC 3010259. PMID 20871596.
  41. Liu, Feng; Barsyte-Lovejoy, Dalia; Li, Fengling; Xiong, Yan; Korboukh, Victoria; Huang, Xi-Ping; Allali-Hassani, Abdellah; Janzen, William P.; Roth, Bryan L.; Frye, Stephen V.; Arrowsmith, Cheryl H. (2013-11-14). "Discovery of an in vivo chemical probe of the lysine methyltransferases G9a and GLP". Journal of Medicinal Chemistry. 56 (21): 8931–8942. doi:10.1021/jm401480r. ISSN 1520-4804. PMC 3880643. PMID 24102134.
  42. Konze, Kyle D.; Ma, Anqi; Li, Fengling; Barsyte-Lovejoy, Dalia; Parton, Trevor; Macnevin, Christopher J.; Liu, Feng; Gao, Cen; Huang, Xi-Ping; Kuznetsova, Ekaterina; Rougie, Marie (2013). "An orally bioavailable chemical probe of the Lysine Methyltransferases EZH2 and EZH1". ACS Chemical Biology. 8 (6): 1324–1334. doi:10.1021/cb400133j. ISSN 1554-8937. PMC 3773059. PMID 23614352.
  43. Bonday, Zahid Q.; Cortez, Guillermo S.; Grogan, Michael J.; Antonysamy, Stephen; Weichert, Ken; Bocchinfuso, Wayne P.; Li, Fengling; Kennedy, Steven; Li, Binghui; Mader, Mary M.; Arrowsmith, Cheryl H. (2018-04-23). "LLY-283, a Potent and Selective Inhibitor of Arginine Methyltransferase 5, PRMT5, with Antitumor Activity". ACS Medicinal Chemistry Letters. 9 (7): 612–617. doi:10.1021/acsmedchemlett.8b00014. ISSN 1948-5875. PMC 6047023. PMID 30034588.
  44. Duncan, Kenneth W.; Rioux, Nathalie; Boriack-Sjodin, P. Ann; Munchhof, Michael J.; Reiter, Lawrence A.; Majer, Christina R.; Jin, Lei; Johnston, L. Danielle; Chan-Penebre, Elayne; Kuplast, Kristy G.; Porter Scott, Margaret (2016-02-11). "Structure and Property Guided Design in the Identification of PRMT5 Tool Compound EPZ015666". ACS Medicinal Chemistry Letters. 7 (2): 162–166. doi:10.1021/acsmedchemlett.5b00380. ISSN 1948-5875. PMC 4753547. PMID 26985292.
  45. Grebien, Florian; Vedadi, Masoud; Getlik, Matthäus; Giambruno, Roberto; Grover, Amit; Avellino, Roberto; Skucha, Anna; Vittori, Sarah; Kuznetsova, Ekaterina; Smil, David; Barsyte-Lovejoy, Dalia (August 2015). "Pharmacological targeting of the Wdr5-MLL interaction in C/EBPα N-terminal leukemia". Nature Chemical Biology. 11 (8): 571–578. doi:10.1038/nchembio.1859. ISSN 1552-4469. PMC 4511833. PMID 26167872.
  46. Roskoski, Robert (June 2019). "Properties of FDA-approved small molecule protein kinase inhibitors". Pharmacological Research. 144: 19–50. doi:10.1016/j.phrs.2019.03.006. ISSN 1096-1186. PMID 30877063. S2CID 80625382.
  47. Wilson, LJ; et, al. (2018). "New Perspectives, Opportunitiess, and Challenges in Exploring the Human Protein Kinome". Cancer Research. 78 (1): 15–29. doi:10.1158/0008-5472.CAN-17-2291. PMID 29254998.
  48. Sorget, Nienke; et, al (2020). "Exploring the understudied human kinome for research and therapeutic opportunities" (PDF). www.biorxiv.org. doi:10.1101/2020.04.02.022277. S2CID 215404186.
  49. Buljan, M; et, al. (2020). "Kinase Interaction Network Expands Functional and Disease Roles of Human Kinases". Molecular Cell. 79 (3): 504–520.e9. doi:10.1016/j.molcel.2020.07.001. PMC 7427327. PMID 32707033. S2CID 220746851.
  50. "Target Enabling Packages (TEPs)". SGC. 2016-06-13. Retrieved 2020-09-09.
  51. Edwards, Aled M.; Arrowsmith, Cheryl H.; Bountra, Chas; Bunnage, Mark E.; Feldmann, Marc; Knight, Julian C.; Patel, Dhavalkumar D.; Prinos, Panagiotis; Taylor, Michael D.; Sundström, Michael; SGC Open Source Target-Discovery Partnership (March 2015). "Preclinical target validation using patient-derived cells". Nature Reviews. Drug Discovery. 14 (3): 149–150. doi:10.1038/nrd4565. ISSN 1474-1784. PMID 25722227. S2CID 2423838.
  52. "Viral Interruption Medicines Initiative (VIMI)". Viral Interruption Medicines Initiative (VIMI). Retrieved 2021-03-21.
  53. Hoag, Hannah (2009). "Richard Gold". Nature Biotechnology. 27 (5): 409. doi:10.1038/nbt0509-409. ISSN 1546-1696. PMID 19430435. S2CID 34394262.
  54. Edwards, Aled; Morgan, Max; Al Chawaf, Arij; Andrusiak, Kerry; Charney, Rachel; Cynader, Zarya; ElDessouki, Ahmed; Lee, Yunjeong; Moeser, Andrew; Stern, Simon; Zuercher, William J. (31 May 2017). "A trust approach for sharing research reagents". Science Translational Medicine. 9 (392): eaai9055. doi:10.1126/scitranslmed.aai9055. ISSN 1946-6242. PMID 28566431. S2CID 4020927.
  55. "Chemical Probes". SGC. 2019-04-08. Retrieved 2020-09-09.
  56. Harding, Rachel (19 October 2016). "An Open Approach to Huntington's Disease Research". nature blogs.
  57. Vedadi, Masoud; Lew, Jocelyne; Artz, Jennifer; Amani, Mehrnaz; Zhao, Yong; Dong, Aiping; Wasney, Gregory A.; Gao, Mian; Hills, Tanya; Brokx, Stephen; Qiu, Wei (January 2007). "Genome-scale protein expression and structural biology of Plasmodium falciparum and related Apicomplexan organisms". Molecular and Biochemical Parasitology. 151 (1): 100–110. doi:10.1016/j.molbiopara.2006.10.011. ISSN 0166-6851. PMID 17125854.
  58. Frye, Stephen V.; Arkin, Michelle R.; Arrowsmith, Cheryl H.; Conn, P. Jeffrey; Glicksman, Marcie A.; Hull-Ryde, Emily A.; Slusher, Barbara S. (November 2015). "Tackling reproducibility in academic preclinical drug discovery". Nature Reviews. Drug Discovery. 14 (11): 733–734. doi:10.1038/nrd4737. ISSN 1474-1784. PMID 26388229. S2CID 205478934.
  59. Marcon, Edyta; Jain, Harshika; Bhattacharya, Anandi; Guo, Hongbo; Phanse, Sadhna; Pu, Shuye; Byram, Gregory; Collins, Ben C.; Dowdell, Evan; Fenner, Maria; Guo, Xinghua (August 2015). "Assessment of a method to characterize antibody selectivity and specificity for use in immunoprecipitation". Nature Methods. 12 (8): 725–731. doi:10.1038/nmeth.3472. ISSN 1548-7105. PMID 26121405. S2CID 205423964.
  60. Gruetter, Markus (2012). "Open collaboration is key to new drugs". Nature. 491 (7422): 40. doi:10.1038/491040d. ISSN 0028-0836. PMID 23128216. S2CID 205074791.
  61. Carter, Adrian J.; Kraemer, Oliver; Zwick, Matthias; Mueller-Fahrnow, Anke; Arrowsmith, Cheryl H.; Edwards, Aled M. (November 2019). "Target 2035: probing the human proteome". Drug Discovery Today. 24 (11): 2111–2115. doi:10.1016/j.drudis.2019.06.020. ISSN 1878-5832. PMID 31278990.
  62. Schapira, Matthieu; Tyers, Mike; Torrent, Maricel; Arrowsmith, Cheryl H. (November 2017). "WD40 repeat domain proteins: a novel target class?". Nature Reviews. Drug Discovery. 16 (11): 773–786. doi:10.1038/nrd.2017.179. ISSN 1474-1784. PMC 5975957. PMID 29026209.
  63. Song, Richard; Wang, Zhong-Duo; Schapira, Matthieu (6 October 2017). "Disease Association and Druggability of WD40 Repeat Proteins". Journal of Proteome Research. 16 (10): 3766–3773. doi:10.1021/acs.jproteome.7b00451. ISSN 1535-3907. PMID 28956604.
  64. Wang, Jiayan; Yazdani, Setayesh; Han, Ana; Schapira, Matthieu (March 2020). "Structure-based view of the druggable genome". Drug Discovery Today. 25 (3): 561–567. doi:10.1016/j.drudis.2020.02.006. ISSN 1878-5832. PMID 32084498. S2CID 211246313.
  65. Wacker, Daniel; Stevens, Raymond C.; Roth, Bryan L. (2017-07-27). "How Ligands Illuminate GPCR Molecular Pharmacology". Cell. 170 (3): 414–427. doi:10.1016/j.cell.2017.07.009. ISSN 1097-4172. PMC 5560499. PMID 28753422.
  66. Roth, Bryan L.; Irwin, John J.; Shoichet, Brian K. (November 2017). "Discovery of new GPCR ligands to illuminate new biology". Nature Chemical Biology. 13 (11): 1143–1151. doi:10.1038/nchembio.2490. ISSN 1552-4469. PMC 5835362. PMID 29045379.
  67. Roth, Bryan L. (August 2019). "How structure informs and transforms chemogenetics". Current Opinion in Structural Biology. 57: 9–16. doi:10.1016/j.sbi.2019.01.016. ISSN 1879-033X. PMID 30818201. S2CID 73479428.
  68. Edwards, Aled (2016-03-17). "Reproducibility: Team up with industry". Nature. 531 (7594): 299–301. Bibcode:2016Natur.531..299E. doi:10.1038/531299a. ISSN 1476-4687. PMID 26983524. S2CID 4467772.
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