Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 13-21 |
| Number of pages | 9 |
| Journal | RSC Medicinal Chemistry |
| Volume | 13 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 1 Jan 2022 |
Cite this
- APA
- Author
- BIBTEX
- Harvard
- Standard
- RIS
- Vancouver
}
In: RSC Medicinal Chemistry, Vol. 13, No. 1, 01.01.2022, p. 13-21.
Research output: Contribution to journal › Article › Other › peer-review
TY - JOUR
T1 - Target 2035-update on the quest for a probe for every protein
AU - Müller, Susanne
AU - Ackloo, Suzanne
AU - Al Chawaf, Arij
AU - Al-Lazikani, Bissan
AU - Antolin, Albert
AU - Baell, Jonathan B.
AU - Beck, Hartmut
AU - Beedie, Shaunna
AU - Betz, Ulrich A.K.
AU - Bezerra, Gustavo Arruda
AU - Brennan, Paul E.
AU - Brown, David
AU - Brown, Peter J.
AU - Bullock, Alex N.
AU - Carter, Adrian J.
AU - Chaikuad, Apirat
AU - Chaineau, Mathilde
AU - Ciulli, Alessio
AU - Collins, Ian
AU - Dreher, Jan
AU - Drewry, David
AU - Edfeldt, Kristina
AU - Edwards, Aled M.
AU - Egner, Ursula
AU - Frye, Stephen V.
AU - Fuchs, Stephen M.
AU - Hall, Matthew D.
AU - Hartung, Ingo V.
AU - Hillisch, Alexander
AU - Hitchcock, Stephen H.
AU - Homan, Evert
AU - Kannan, Natarajan
AU - Kiefer, James R.
AU - Knapp, Stefan
AU - Kostic, Milka
AU - Kubicek, Stefan
AU - Leach, Andrew R.
AU - Lindemann, Sven
AU - Marsden, Brian D.
AU - Matsui, Hisanori
AU - Meier, Jordan L.
AU - Merk, Daniel
AU - Michel, Maurice
AU - Morgan, Maxwell R.
AU - Mueller-Fahrnow, Anke
AU - Owen, Dafydd R.
AU - Perry, Benjamin G.
AU - Rosenberg, Saul H.
AU - Saikatendu, Kumar Singh
AU - Schapira, Matthieu
AU - Scholten, Cora
AU - Sharma, Sujata
AU - Simeonov, Anton
AU - Sundström, Michael
AU - Superti-Furga, Giulio
AU - Todd, Matthew H.
AU - Tredup, Claudia
AU - Vedadi, Masoud
AU - Von Delft, Frank
AU - Willson, Timothy M.
AU - Winter, Georg E.
AU - Workman, Paul
AU - Arrowsmith, Cheryl H.
N1 - Funding Information: 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. Funding Information: The SGC is a registered charity (number 1097737) that receives funds from Bayer Pharma AG, Boehringer Ingelheim, Canada Foundation for Innovation, Eshelman Institute for Innovation, Genentech, Genome Canada through Ontario Genomics Institute [OGI-196], EU/EFPIA/OICR/McGill/KTH/ Diamond Innovative Medicines Initiative 2 Joint Undertaking (EUbOPEN grant number 875510), Janssen, Merck KGaA (aka EMD in Canada and US), Pfizer, Takeda. A. A. A. is primarily supported by a Wellcome Trust Sir Henry Wellcome Postdoctoral Fellowship (204735/Z/16/Z); the People Programme (Marie Curie Actions) of the seventh Framework Program of the European Union (FP7/2007–2013) under REA grant agreement no. 600388 (TECNIOspring program); and the Agency for Business Competitiveness of the Government of Catalonia, ACCIO. B. A.-L., I. C., and P. W. are funded by a Cancer Research UK (CRUK) program grant to the CRUK Cancer Therapeutics Unit (C309/A11566). B. A.-L. and P. W. are funded by a Wellcome Trust biomedical resource and technology grant to sustain and develop the Chemical Probes Portal (212969/Z/18/Z) and a CRUK Drug Discovery Committee strategic award to sustain and develop canSAR (C35696/ A23187). P. W. is a CRUK Life Fellow and is funded by the Chordoma Foundation and Mark Foundation. P. W. and B. A.-L. are members of the CRUK ICR/Imperial Convergence Science Centre (A26234). Institute of Cancer Research (ICR) authors acknowledge infrastructure support from CRUK for the ICR CRUK Centre and NHS funding to the NIHR Biomedical Research Centre at the ICR and Royal Marsden NHS Foundation Trust. M. K. is partly supported by the National Cancer Institute, USA (NCI) T32 CA236754. A. C. laboratory receives funding from the Innovative Medicines Initiative 2 (IMI2) Joint Undertaking under grant agreement No 875510 (EUbOPEN project). A. R. L. acknowledges support from the Member States of the European Molecular Biology Laboratory (EMBL). Publisher Copyright: © 2022 The Royal Society of Chemistry.
PY - 2022/1/1
Y1 - 2022/1/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85124185747&partnerID=8YFLogxK
U2 - 10.1039/d1md00228g
DO - 10.1039/d1md00228g
M3 - Article
AN - SCOPUS:85124185747
SN - 2632-8682
VL - 13
SP - 13
EP - 21
JO - RSC Medicinal Chemistry
JF - RSC Medicinal Chemistry
IS - 1
ER -