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

被引：55

作者：

Mueller, Susanne ^{[1
,2
]}

Ackloo, Suzanne ^{[3
]}

Al Chawaf, Arij ^{[4
]}

Al-Lazikani, Bissan ^{[5
,6
]}

Antolin, Albert ^{[5
,7
]}

Baell, Jonathan B. ^{[8
,9
]}

Beck, Hartmut ^{[10
]}

Beedie, Shaunna ^{[11
]}

Betz, Ulrich A. K. ^{[12
]}

Bezerra, Gustavo Arruda ^{[11
]}

Brennan, Paul E. ^{[13
]}

Brown, David ^{[14
]}

Brown, Peter J. ^{[3
]}

Bullock, Alex N. ^{[11
]}

Carter, Adrian J. ^{[15
]}

Chaikuad, Apirat ^{[1
,2
]}

Chaineau, Mathilde ^{[16
]}

Ciulli, Alessio ^{[17
]}

Collins, Ian ^{[7
]}

Dreher, Jan ^{[10
]}

Drewry, David ^{[18
,19
]}

Edfeldt, Kristina ^{[20
,21
]}

Edwards, Aled M. ^{[3
]}

Egner, Ursula ^{[22
]}

Frye, Stephen, V ^{[19
,23
]}

Fuchs, Stephen M. ^{[24
]}

Hall, Matthew D. ^{[25
]}

Hartung, Ingo, V ^{[26
]}

Hillisch, Alexander ^{[10
]}

Hitchcock, Stephen H. ^{[27
]}

Homan, Evert ^{[28
]}

Kannan, Natarajan ^{[29
,30
]}

Kiefer, James R. ^{[31
]}

Knapp, Stefan ^{[29
,30
]}

Kostic, Milka ^{[32
]}

Kubicek, Stefan ^{[33
]}

Leach, Andrew R. ^{[34
]}

Lindemann, Sven ^{[35
]}

Marsden, Brian D. ^{[11
,36
]}

Matsui, Hisanori ^{[37
]}

Meier, Jordan L. ^{[38
]}

Merk, Daniel ^{[1
,39
]}

Michel, Maurice ^{[28
]}

Morgan, Maxwell R. ^{[3
]}

Mueller-Fahrnow, Anke ^{[22
]}

Owen, Dafydd R. ^{[40
]}

Perry, Benjamin G. ^{[41
]}

Rosenberg, Saul H. ^{[42
]}

Saikatendu, Kumar Singh ^{[43
]}

Schapira, Matthieu ^{[3
,44
]}

机构：

[1] Goethe Univ Frankfurt, Inst Pharmaceut Chem, D-60438 Frankfurt, Germany

[2] Goethe Univ Frankfurt, BMLS, Struct Genom Consortium, D-60438 Frankfurt, Germany

[3] Univ Toronto, Struct Genom Consortium, Toronto, ON M5G 1L7, Canada

[4] Univ Toronto, Toronto, ON M5G 1L7, Canada

[5] Inst Canc Res, Dept Data Sci, London SM2 5NG, England

[6] CRUK ICR Imperial Convergence Sci Ctr, London SM2 5NG, England

[7] Inst Canc Res, Canc Res UK Canc Therapeut Unit, London SM2 5NG, England

[8] Monash Univ, Monash Inst Pharmaceut Sci, Parkville, Vic 3052, Australia

[9] Nanjing Tech Univ, Sch Pharmaceut Sci, 30 South Puzhu Rd, Nanjing 211816, Peoples R China

[10] Bayer AG, Pharmaceut, Res & Dev, D-42103 Wuppertal, Germany

[11] Univ Oxford, Ctr Med Discovery, Old Rd Campus Res Bldg,Roosevelt Dr, Oxford OX3 7DQ, England

[12] Merck KGaA, Darmstadt, Germany

[13] Univ Oxford, Ctr Med Discovery, Alzheimers Res UK Oxford Drug Discovery Inst, Oxford, England

[14] Inst Rech Servier, 125 Chemin Ronde, F-78290 Croissy Sur Seine, France

[15] Boehringer Ingelheim GmbH & Co KG, Discovery Res, D-55216 Ingelheim, Germany

[16] McGill Univ, Montreal Neurol Inst Hosp, Early Drug Discovery Unit EDDU, Montreal, PQ, Canada

[17] Univ Dundee, James Black Ctr, Sch Life Sci, Div Biol Chem & Drug Discovery, Dundee, Scotland

[18] UNC Eshelman Sch Pharm, Struct Genom Consortium, Chapel Hill, NC USA

[19] Univ N Carolina, Sch Med, Dept Med, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA

[20] Karolinska Univ Hosp, Dept Med, Struct Genom Consortium, Stockholm, Sweden

[21] Karolinska Inst, Stockholm, Sweden

[22] Nuvisan Innovat Campus Berlin GmbH, Mullerstr 178, D-13353 Berlin, Germany

[23] Ctr Integrat Chem Biol & Drug Discovery, Eshelman Sch Pharm, Div Chem Biol & Med Chem, Univ North Carolina, Chapel Hill, NC 27599 USA

[24] Inst Prot Innovat, Boston, MA USA

[25] NIH, Natl Ctr Adv Translat Sci, Rockville, MD 20850 USA

[26] Merck Healthcare KGaA, Global R &, Med Chem, Frankfurter Str 250, D-64293 Darmstadt, Germany

[27] Takeda Calif, 9625 Towne Ctr Dr, San Diego, CA 92121 USA

[28] Karolinska Inst, Dept Oncol Pathol, Sci Life Lab, Stockholm, Sweden

[29] Univ Georgia, Inst Bioinformat, Athens, GA 30602 USA

[30] Univ Georgia, Dept Biochem & Mol Biol, Athens, GA 30602 USA

[31] Genentech Inc, South San Francisco, 1 DNA Way, San Francisco, CA 94080 USA

[32] Dana Farber Canc Inst, Dept Canc Biol & Chem Biol Program, 450 Brookline Ave, Boston, MA 02215 USA

[33] Austrian Acad Sci, CeMM Res Ctr Mol Med, Vienna, Austria

[34] European Bioinformat Inst, European Mol Biol Lab, Wellcome Genome Campus, Hinxton CB10 1SD, Cambs, England

[35] Merck Healthcare KGaA, Global R&D, Strateg Innovat, Frankfurter Str 250, D-64293 Darmstadt, Germany

[36] Univ Oxford, Kennedy Inst Rheumatol, NDORMS, Oxford, England

[37] Takeda Pharmaceut Co Ltd, Neurosci Drug Discovery Unit, Res, Fujisawa, Kanagawa, Japan

[38] NCI, Chem Biol Lab, Ctr Canc Res Natl Canc Inst, NIH, Frederick, MD 21701 USA

[39] Ludwig Maximilians Univ Munchen, Chair Pharmaceut & Med Chem, Dept Pharm, D-81377 Munich, Germany

[40] Pfizer Med Design, Discovery Network Grp, Cambridge, MA 02139 USA

[41] Drugs Neglected Dis Initiat, 15 Chemin Camille Vidart, CH-1202 Geneva, Switzerland

[42] AbbVie, N Chicago, IL USA

[43] Takeda Calif Inc, Global Res Externalizat, 9625 Towne Ctr Dr, San Diego, CA 92121 USA

[44] Univ Toronto, Dept Pharmacol & Toxicol, Toronto, ON M5S 1A8, Canada

[45] Bayer AG, Pharmaceut, Res & Dev, D-13353 Berlin, Germany

[46] Janssen Res & Dev, Discovery Sci, Struct & Prot Sci, 1400 McKean Rd, Spring House, PA 19477 USA

[47] Karolinska Univ Hosp, Dept Med Solna, Div Rheumatol, Stockholm, Sweden

[48] Med Univ Vienna, Ctr Physiol & Pharmacol, Vienna, Austria

[49] UCL, Sch Pharm, London WC1N 1AX, England

[50] Diamond Light Source Ltd, Hanvell Sci & Innovat Confirms, Didcot OX11 0QX, Oxon, England

来源：

RSC MEDICINAL CHEMISTRY | 2022年 / 13卷 / 01期

基金：

英国惠康基金; 加拿大创新基金会;

关键词：

DRUG DISCOVERY;

D O I：

10.1039/d1md00228g

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 (similar to 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.

引用

页码：13 / 21

页数：10

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