Müller Susanne, Ackloo Suzanne, Al Chawaf Arij, Al-Lazikani Bissan, Antolin Albert, Baell Jonathan B, Beck Hartmut, Beedie Shaunna, Betz Ulrich A K, Bezerra Gustavo Arruda, Brennan Paul E, Brown David, Brown Peter J, Bullock Alex N, Carter Adrian J, Chaikuad Apirat, Chaineau Mathilde, Ciulli Alessio, Collins Ian, Dreher Jan, Drewry David, Edfeldt Kristina, Edwards Aled M, Egner Ursula, Frye Stephen V, Fuchs Stephen M, Hall Matthew D, Hartung Ingo V, Hillisch Alexander, Hitchcock Stephen H, Homan Evert, Kannan Natarajan, Kiefer James R, Knapp Stefan, Kostic Milka, Kubicek Stefan, Leach Andrew R, Lindemann Sven, Marsden Brian D, Matsui Hisanori, Meier Jordan L, Merk Daniel, Michel Maurice, Morgan Maxwell R, Mueller-Fahrnow Anke, Owen Dafydd R, Perry Benjamin G, Rosenberg Saul H, Saikatendu Kumar Singh, Schapira Matthieu, Scholten Cora, Sharma Sujata, Simeonov Anton, Sundström Michael, Superti-Furga Giulio, Todd Matthew H, Tredup Claudia, Vedadi Masoud, von Delft Frank, Willson Timothy M, Winter Georg E, Workman Paul, Arrowsmith Cheryl H
Institute of Pharmaceutical Chemistry, Goethe University Frankfurt Frankfurt 60438 Germany.
Structural Genomics Consortium, BMLS, Goethe University Frankfurt Frankfurt 60438 Germany
RSC Med Chem. 2021 Dec 3;13(1):13-21. doi: 10.1039/d1md00228g. eCollection 2022 Jan 27.
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.
人类基因组初稿发布二十年后，我们对人类蛋白质组的了解仍然支离破碎。将基因组学中丰富的新知识转化为新药面临的挑战在于，执行生物功能的主要是蛋白质而非基因。因此，必须通过蛋白质功能这一视角来理解生物学在健康和疾病中的运作方式。相应地，几个世纪以来，人类蛋白质的一个子集一直是科学家研究兴趣的核心，我们已经积累了关于约65%的人类蛋白质组的不同程度的知识。然而，人类蛋白质组中很大一部分（约35%）仍未得到表征，且成功用于药物研发的人类蛋白质组不到5%。这凸显了我们获取遗传信息的能力与后续有效药物开发之间的巨大脱节。“2035目标”是一个由公共和私营部门的生物医学科学家组成的国际联盟，旨在通过开发和应用新技术来填补这一差距，以便到2035年为整个人类蛋白质组创建化学基因组文库、化学探针和/或生物探针。
