Target 2035 – update on the quest for a probe for every protein
* Corresponding authors
a Institute of Pharmaceutical Chemistry, Goethe University Frankfurt, Frankfurt 60438, Germany
b
Structural Genomics Consortium, BMLS, Goethe University Frankfurt, Frankfurt 60438, Germany
E-mail:
susanne.mueller-knapp@bmls.de
c
Structural Genomics Consortium, University of Toronto, Toronto, Ontario, Canada
E-mail:
Cheryl.Arrowsmith@uhnresearch.ca
d University of Toronto, Toronto, Ontario, Canada
e Department of Data Science, The Institute of Cancer Research, London, UK
f CRUK ICR/Imperial Convergence Science Centre, London, UK
g Cancer Research UK Cancer Therapeutics Unit, The Institute of Cancer Research, London SM2 5NG, UK
h Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia
i School of Pharmaceutical Sciences, Nanjing Tech University, No. 30 South Puzhu Road, Nanjing 211816, People's Republic of China
j Research and Development, Bayer AG, Pharmaceuticals, 42103 Wuppertal, Germany
k Centre for Medicines Discovery, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford OX3 7DQ, UK
l Merck KGaA, Darmstadt, Germany
m Alzheimer's Research UK Oxford Drug Discovery Institute, Centre for Medicines Discovery, University of Oxford, Oxford, UK
n Institut Recherches de Servier, 125 Chemin de Ronde, 78290 Croissy, France
o Discovery Research, Boehringer Ingelheim, 55216 Ingelheim am Rhein, Germany
p Early Drug Discovery Unit (EDDU), Montreal Neurological Institute-Hospital, McGill University, Montreal, QC, Canada
q School of Life Sciences, Division of Biological Chemistry and Drug Discovery, University of Dundee, James Black Centre, Dundee, UK
r Structural Genomics Consortium, UNC Eshelman School of Pharmacy, Chapel Hill, NC, USA
s Lineberger Comprehensive Cancer Center, Department of Medicine, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
t Structural Genomics Consortium, Department of Medicine, Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden
u Nuvisan Innovation Campus Berlin GmbH, Müllerstraße 178, Berlin, Germany
v 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, USA
w Institute for Protein Innovation, Boston, MA, USA
x National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland 20850, USA
y Medicinal Chemistry, Global R&D, Merck Healthcare KGaA, Frankfurter Straße 250, Darmstadt, Germany
z Takeda California, 9625 Towne Centre Drive, San Diego, California 92121, USA
aa Science for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden
ab Institute of Bioinformatics and Department of Biochemistry and Molecular Biology, University of Georgia, Athens, GA, USA
ac Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, USA
ad Department of Cancer Biology and Chemical Biology Program, Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA 02215, USA
ae CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria
af European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridgeshire CB10 1SD, UK
ag Strategic Innovation, Global R&D, Merck Healthcare KGaA, Frankfurter Straße 250, Darmstadt, Germany
ah Kennedy Institute of Rheumatology, NDORMS, University of Oxford, UK
ai Neuroscience Drug Discovery Unit, Research, Takeda Pharmaceutical Company Limited, Fujisawa, Kanagawa, Japan
aj Chemical Biology Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD, USA
ak LMU Munich, Department of Pharmacy, Chair of Pharmaceutical and Medicinal Chemistry, 81377 Munich, Germany
al Discovery Network Group, Pfizer Medicine Design, Cambridge, MA 02139, USA
am Drugs for Neglected Diseases initiative, 15 Chemin Camille Vidart, Geneva 1202, Switzerland
an AbbVie, North Chicago, Illinois, USA
ao Global Research Externalization, Takeda California, Inc., 9625 Towne Center Drive, San Diego, CA 92121, USA
ap Department of Pharmacology & Toxicology, University of Toronto, Toronto, Ontario M5S 1A8, Canada
aq Research and Development, Bayer AG, Pharmaceuticals, 13353 Berlin, Germany
ar Structural & Protein Sciences, Discovery Sciences, Janssen Research & Development, 1400 McKean Rd, Spring House, PA 19477, USA
as Division of Rheumatology, Department of Medicine Solna, Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden
at Center for Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria
au School of Pharmacy, University College London, London, UK
av Diamond Light Source Ltd, Harwell Science and Innovation Campus, Didcot OX11 0QX, UK
aw Department of Biochemistry, University of Johannesburg, Auckland Park 2006, South Africa
ax Research Complex at Harwell, Harwell Science and Innovation Campus, Didcot OX11 0FA, UK
ay Princess Margaret Cancer Centre, Toronto, Ontario, Canada
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.