Target 2035 - update on the quest for a probe for every protein.

Autor:	Müller S; Institute of Pharmaceutical Chemistry, Goethe University Frankfurt Frankfurt 60438 Germany.; Structural Genomics Consortium, BMLS, Goethe University Frankfurt Frankfurt 60438 Germany susanne.mueller-knapp@bmls.de., Ackloo S; Structural Genomics Consortium, University of Toronto Toronto Ontario M5G 1L7 Canada Cheryl.Arrowsmith@uhnresearch.ca., Al Chawaf A; University of Toronto Toronto Ontario M5G 1L7 Canada., Al-Lazikani B; Department of Data Science, The Institute of Cancer Research London SM2 5NG UK.; CRUK ICR/Imperial Convergence Science Centre London SM2 5NG UK., Antolin A; Department of Data Science, The Institute of Cancer Research London SM2 5NG UK.; Cancer Research UK Cancer Therapeutics Unit, The Institute of Cancer Research London SM2 5NG UK., Baell JB; Monash Institute of Pharmaceutical Sciences, Monash University Parkville Victoria 3052 Australia.; School of Pharmaceutical Sciences, Nanjing Tech University No. 30 South Puzhu Road Nanjing 211816 People's Republic of China., Beck H; Research and Development, Bayer AG, Pharmaceuticals 42103 Wuppertal Germany., Beedie S; Centre for Medicines Discovery, University of Oxford Old Road Campus Research Building, Roosevelt Drive Oxford OX3 7DQ UK., Betz UAK; Merck KGaA Darmstadt Germany., Bezerra GA; Centre for Medicines Discovery, University of Oxford Old Road Campus Research Building, Roosevelt Drive Oxford OX3 7DQ UK., Brennan PE; Alzheimer's Research UK Oxford Drug Discovery Institute, Centre for Medicines Discovery, University of Oxford Oxford OX3 7FZ UK., Brown D; Institut Recherches de Servier 125 Chemin de Ronde 78290 Croissy France., Brown PJ; Structural Genomics Consortium, University of Toronto Toronto Ontario M5G 1L7 Canada Cheryl.Arrowsmith@uhnresearch.ca., Bullock AN; Centre for Medicines Discovery, University of Oxford Old Road Campus Research Building, Roosevelt Drive Oxford OX3 7DQ UK., Carter AJ; Discovery Research, Boehringer Ingelheim 55216 Ingelheim am Rhein Germany., Chaikuad A; Institute of Pharmaceutical Chemistry, Goethe University Frankfurt Frankfurt 60438 Germany.; Structural Genomics Consortium, BMLS, Goethe University Frankfurt Frankfurt 60438 Germany susanne.mueller-knapp@bmls.de., Chaineau M; Early Drug Discovery Unit (EDDU), Montreal Neurological Institute-Hospital, McGill University Montreal QC Canada., Ciulli A; School of Life Sciences, Division of Biological Chemistry and Drug Discovery, University of Dundee James Black Centre Dundee UK., Collins I; Cancer Research UK Cancer Therapeutics Unit, The Institute of Cancer Research London SM2 5NG UK., Dreher J; Research and Development, Bayer AG, Pharmaceuticals 42103 Wuppertal Germany., Drewry D; Structural Genomics Consortium, UNC Eshelman School of Pharmacy Chapel Hill NC USA.; Lineberger Comprehensive Cancer Center, Department of Medicine, School of Medicine, University of North Carolina at Chapel Hill Chapel Hill NC 27599 USA., Edfeldt K; Structural Genomics Consortium, Department of Medicine, Karolinska University Hospital and Karolinska Institutet Stockholm Sweden., Edwards AM; Structural Genomics Consortium, University of Toronto Toronto Ontario M5G 1L7 Canada Cheryl.Arrowsmith@uhnresearch.ca., Egner U; Nuvisan Innovation Campus Berlin GmbH Müllerstraße 178 13353 Berlin Germany., Frye SV; Lineberger Comprehensive Cancer Center, Department of Medicine, School of Medicine, University of North Carolina at Chapel Hill Chapel Hill NC 27599 USA.; Center for Integrative Chemical Biology and Drug Discovery, Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill Chapel Hill NC 27599 USA., Fuchs SM; Institute for Protein Innovation Boston MA USA., Hall MD; National Center for Advancing Translational Sciences, National Institutes of Health Rockville Maryland 20850 USA., Hartung IV; Medicinal Chemistry, Global R&D, Merck Healthcare KGaA Frankfurter Straße 250 64293 Darmstadt Germany., Hillisch A; Research and Development, Bayer AG, Pharmaceuticals 42103 Wuppertal Germany., Hitchcock SH; Takeda California 9625 Towne Centre Drive San Diego California 92121 USA., Homan E; Science for Life Laboratory, Department of Oncology-Pathology Karolinska Institutet Stockholm Sweden., Kannan N; Institute of Bioinformatics and Department of Biochemistry and Molecular Biology, University of Georgia Athens GA USA., Kiefer JR; Genentech, Inc. 1 DNA Way South San Francisco California 94080 USA., Knapp S; Institute of Pharmaceutical Chemistry, Goethe University Frankfurt Frankfurt 60438 Germany.; Structural Genomics Consortium, BMLS, Goethe University Frankfurt Frankfurt 60438 Germany susanne.mueller-knapp@bmls.de., Kostic M; Department of Cancer Biology and Chemical Biology Program, Dana-Farber Cancer Institute 450 Brookline Ave Boston MA 02215 USA., Kubicek S; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences Vienna Austria., Leach AR; European Molecular Biology Laboratory, European Bioinformatics Institute Wellcome Genome Campus, Hinxton Cambridgeshire CB10 1SD UK., Lindemann S; Strategic Innovation, Global R&D, Merck Healthcare KGaA Frankfurter Straße 250 64293 Darmstadt Germany., Marsden BD; Centre for Medicines Discovery, University of Oxford Old Road Campus Research Building, Roosevelt Drive Oxford OX3 7DQ UK.; Kennedy Institute of Rheumatology, NDORMS, University of Oxford UK., Matsui H; Neuroscience Drug Discovery Unit, Research, Takeda Pharmaceutical Company Limited Fujisawa Kanagawa Japan., Meier JL; Chemical Biology Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health Frederick MD USA., Merk D; Institute of Pharmaceutical Chemistry, Goethe University Frankfurt Frankfurt 60438 Germany.; LMU Munich, Department of Pharmacy, Chair of Pharmaceutical and Medicinal Chemistry 81377 Munich Germany., Michel M; Science for Life Laboratory, Department of Oncology-Pathology Karolinska Institutet Stockholm Sweden., Morgan MR; Structural Genomics Consortium, University of Toronto Toronto Ontario M5G 1L7 Canada Cheryl.Arrowsmith@uhnresearch.ca., Mueller-Fahrnow A; Nuvisan Innovation Campus Berlin GmbH Müllerstraße 178 13353 Berlin Germany., Owen DR; Discovery Network Group, Pfizer Medicine Design Cambridge MA 02139 USA., Perry BG; Drugs for Neglected Diseases initiative 15 Chemin Camille Vidart Geneva 1202 Switzerland., Rosenberg SH; AbbVie North Chicago Illinois USA., Saikatendu KS; Global Research Externalization, Takeda California, Inc. 9625 Towne Center Drive San Diego CA 92121 USA., Schapira M; Structural Genomics Consortium, University of Toronto Toronto Ontario M5G 1L7 Canada Cheryl.Arrowsmith@uhnresearch.ca.; Department of Pharmacology & Toxicology, University of Toronto Toronto Ontario M5S 1A8 Canada., Scholten C; Research and Development, Bayer AG, Pharmaceuticals 13353 Berlin Germany., Sharma S; Structural & Protein Sciences, Discovery Sciences, Janssen Research & Development 1400 McKean Rd Spring House PA 19477 USA., Simeonov A; National Center for Advancing Translational Sciences, National Institutes of Health Rockville Maryland 20850 USA., Sundström M; Division of Rheumatology, Department of Medicine Solna, Karolinska University Hospital and Karolinska Institutet Stockholm Sweden., Superti-Furga G; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences Vienna Austria.; Center for Physiology and Pharmacology, Medical University of Vienna Vienna Austria., Todd MH; School of Pharmacy, University College London London WC1N 1AX UK., Tredup C; Institute of Pharmaceutical Chemistry, Goethe University Frankfurt Frankfurt 60438 Germany.; Structural Genomics Consortium, BMLS, Goethe University Frankfurt Frankfurt 60438 Germany susanne.mueller-knapp@bmls.de., Vedadi M; Structural Genomics Consortium, University of Toronto Toronto Ontario M5G 1L7 Canada Cheryl.Arrowsmith@uhnresearch.ca.; Department of Pharmacology & Toxicology, University of Toronto Toronto Ontario M5S 1A8 Canada., von Delft F; Centre for Medicines Discovery, University of Oxford Old Road Campus Research Building, Roosevelt Drive Oxford OX3 7DQ UK.; Diamond Light Source Ltd Harwell Science and Innovation Campus Didcot OX11 0QX UK.; Department of Biochemistry, University of Johannesburg Auckland Park 2006 South Africa.; Research Complex at Harwell Harwell Science and Innovation Campus Didcot OX11 0FA UK., Willson TM; Lineberger Comprehensive Cancer Center, Department of Medicine, School of Medicine, University of North Carolina at Chapel Hill Chapel Hill NC 27599 USA., Winter GE; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences Vienna Austria., Workman P; CRUK ICR/Imperial Convergence Science Centre London SM2 5NG UK.; Cancer Research UK Cancer Therapeutics Unit, The Institute of Cancer Research London SM2 5NG UK., Arrowsmith CH; Structural Genomics Consortium, University of Toronto Toronto Ontario M5G 1L7 Canada Cheryl.Arrowsmith@uhnresearch.ca.; Princess Margaret Cancer Centre Toronto Ontario M5G 1L7 Canada.
Jazyk:	angličtina
Zdroj:	RSC medicinal chemistry [RSC Med Chem] 2021 Dec 03; Vol. 13 (1), pp. 13-21. Date of Electronic Publication: 2021 Dec 03 (Print Publication: 2022).
DOI:	10.1039/d1md00228g
Abstrakt:	Twenty years after the publication of the first draft of the human genome, our knowledge of the human proteome is still fragmented. The challenge of translating the wealth of new knowledge from genomics into new medicines is that proteins, and not genes, are the primary executers of biological function. Therefore, much of how biology works in health and disease must be understood through the lens of protein function. Accordingly, a subset of human proteins has been at the heart of research interests of scientists over the centuries, and we have accumulated varying degrees of knowledge about approximately 65% of the human proteome. Nevertheless, a large proportion of proteins in the human proteome (∼35%) remains uncharacterized, and less than 5% of the human proteome has been successfully targeted for drug discovery. This highlights the profound disconnect between our abilities to obtain genetic information and subsequent development of effective medicines. Target 2035 is an international federation of biomedical scientists from the public and private sectors, which aims to address this gap by developing and applying new technologies to create by year 2035 chemogenomic libraries, chemical probes, and/or biological probes for the entire human proteome. Competing Interests: A. A. A., B. A.-L., I. C., and P. W. are employees of the Institute of Cancer Research (ICR) which operates a Rewards to Inventors scheme whereby employees of the ICR may receive financial benefit following commercial licensing of their research. P. W. is a consultant/scientific advisory board member for Nextech Invest Ltd, Storm Therapeutics, Astex Pharmaceuticals, Black Diamond Therapeutics, CV6 and Vividion Therapeutics, and holds stock in Chroma Therapeutics, NextInvest, and Storm Therapeutics. P. W. is also a non-executive director of Storm Therapeutics and the Royal Marsden NHS Trust; a board member and executive director of the non-profit Chemical Probes Portal; and a former employee of AstraZeneca. P. W. has received research funding from Vernalis, Astex Therapeutics, Merck KGaA, BACIT/Sixth Element Capital/CRT Pioneer Fund. B. A.-L. is/was a consultant/scientific advisory board member for GSK, Open Targets, Astex Pharmaceuticals, Nuvectis Pharma and Astellas Pharma, and is an ex-employee of Inpharmatica Ltd. A. A. A., B. A.-L., and P. W. have been instrumental in the creation/development of canSAR and Probe Miner. B. A.-L. was instrumental in the creation of ChEMBL and is a director of the non-profit Chemical Probes Portal. I. C. is/was a consultant to Epidarex LLP, AdoRx Therapeutics, and Enterprise Therapeutics, and is a director of the non-profit Chemical Probes Portal. I. C. has received research funding from Astex, Merck KGaA, Janssen Biopharma, Monte Rosa Therapeutics, and Sixth Element Capital/CRT Pioneer Fund. I. C. holds stock in Monte Rosa Therapeutics AG and is a former employee of Merck Sharp & Dohme. M. K. is a paid consultant for Life Science Editors (LSE). A. C. receives or has received sponsored research support from Almirall, Amphista therapeutics, Boehringer Ingelheim, Eisai, Nurix therapeutics, and Ono Pharmaceuticals. A. C. is a scientific founder, shareholder, and consultant of Amphista therapeutics. A. R. L. has consulted for Astex Therapeutics and has received research funding from Novo Nordisk. S. Ku. is a co-founder and shareholder of Proxygen GmbH and Solgate GmbH. G. E. W. is a founder and shareholder of Proxygen and Solgate Therapeutics. He is on the Research Review Committee of Almirall and coordinates a research collaboration between CeMM and Pfizer. S. F. reports equity ownership and membership on the Meryx Board of Directors and consulting or SAB relationships with Artios, Astex, Cullgen, Design Therapeutics, Flare, Mitokinin, Pathios, ReViral and eFFector. This communication reflects the views of the authors and neither IMI nor the European Union, EFPIA or any Associated Partners are liable for any use that may be made of the information contained herein. (This journal is © The Royal Society of Chemistry.)
Databáze:	MEDLINE
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