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X-ray screening identifies active site and allosteric inhibitors of SARS-CoV-2 main protease 期刊论文
Science, 2021
作者:  Sebastian Günther;  Patrick Y. A. Reinke;  Yaiza Fernández-García;  Julia Lieske;  Thomas J. Lane;  Helen M. Ginn;  Faisal H. M. Koua;  Christiane Ehrt;  Wiebke Ewert;  Dominik Oberthuer;  Oleksandr Yefanov;  Susanne Meier;  Kristina Lorenzen;  Boris Krichel;  Janine-Denise Kopicki;  Luca Gelisio;  Wolfgang Brehm;  Ilona Dunkel;  Brandon Seychell;  Henry Gieseler;  Brenna Norton-Baker;  Beatriz Escudero-Pérez;  Martin Domaracky;  Sofiane Saouane;  Alexandra Tolstikova;  Thomas A. White;  Anna Hänle;  Michael Groessler;  Holger Fleckenstein;  Fabian Trost;  Marina Galchenkova;  Yaroslav Gevorkov;  Chufeng Li;  Salah Awel;  Ariana Peck;  Miriam Barthelmess;  Frank Schlünzen;  P. Lourdu Xavier;  Nadine Werner;  Hina Andaleeb;  Najeeb Ullah;  Sven Falke;  Vasundara Srinivasan;  Bruno Alves França;  Martin Schwinzer;  Hévila Brognaro;  Cromarte Rogers;  Diogo Melo;  Joanna J. Zaitseva-Doyle;  Juraj Knoska;  Gisel E. Peña-Murillo;  Aida Rahmani Mashhour;  Vincent Hennicke;  Pontus Fischer;  Johanna Hakanpää;  Jan Meyer;  Philip Gribbon;  Bernhard Ellinger;  Maria Kuzikov;  Markus Wolf;  Andrea R. Beccari;  Gleb Bourenkov;  David von Stetten;  Guillaume Pompidor;  Isabel Bento;  Saravanan Panneerselvam;  Ivars Karpics;  Thomas R. Schneider;  Maria Marta Garcia-Alai;  Stephan Niebling;  Christian Günther;  Christina Schmidt;  Robin Schubert;  Huijong Han;  Juliane Boger;  Diana C. F. Monteiro;  Linlin Zhang;  Xinyuanyuan Sun;  Jonathan Pletzer-Zelgert;  Jan Wollenhaupt;  Christian G. Feiler;  Manfred S. Weiss;  Eike-Christian Schulz;  Pedram Mehrabi;  Katarina Karničar;  Aleksandra Usenik;  Jure Loboda;  Henning Tidow;  Ashwin Chari;  Rolf Hilgenfeld;  Charlotte Uetrecht;  Russell Cox;  Andrea Zaliani;  Tobias Beck;  Matthias Rarey;  Stephan Günther;  Dusan Turk;  Winfried Hinrichs;  Henry N. Chapman;  Arwen R. Pearson;  Christian Betzel;  Alke Meents
收藏  |  浏览/下载:17/0  |  提交时间:2021/05/14
Multispecific drugs herald a new era of biopharmaceutical innovation 期刊论文
NATURE, 2020, 580 (7803) : 329-338
作者:  Gallego, Laura D.;  Schneider, Maren;  Mittal, Chitvan;  Romanauska, Anete;  Carrillo, Ricardo M. Gudino;  Schubert, Tobias;  Pugh, B. Franklin;  Koehler, Alwin
收藏  |  浏览/下载:31/0  |  提交时间:2020/07/03

The modern biopharmaceutical industry traces its roots to the dawn of the twentieth century, coincident with marketing of aspirin-a signature event in the history of modern drug development. Although the archetypal discovery process did not change markedly in the first seven decades of the industry, the past fifty years have seen two successive waves of transformative innovation in the development of drug molecules: the rise of '  rational drug discovery'  methodology in the 1970s, followed by the invention of recombinant protein-based therapeutic agents in the 1980s. An incipient fourth wave is the advent of multispecific drugs. The successful development of prospectively designed multispecific drugs has the potential to reconfigure our ideas of how target-based therapeutic molecules can work, and what it is possible to achieve with them. Here I review the two major classes of multispecific drugs: those that enrich a therapeutic agent at a particular site of action and those that link a therapeutic target to a biological effector. The latter class-being freed from the constraint of having to directly modulate the target upon binding-may enable access to components of the proteome that currently cannot be targeted by drugs.