Successful Drug Discovery, Volume 5

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Volume 5

Edited by

János Fischer Christian Klein Wayne E. Childers

Editors

János Fischer

Richter Co., Plc.

Pharma Research

Gyömröi ut 19/21

1103 Budapest

Hungary

Christian Klein

Roche Innovation Center Zurich

Cancer Immunotherapy Discovery

Wagistrasse 10

8952 Schlieren

Switzerland

Wayne E. Childers

Temple University School of Pharmacy

Moulder Ctr. for Drug Discovery Res.

3307 N Broad Street

PA

United States

Cover

Supported by the

International Union of Pure and Applied Chemistry (IUPAC)

Chemistry and Human Health Division

PO Box 13757

Research Triangle Park, NC 2770‐3757

USA

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© 2021 WILEY‐VCH GmbH, Boschstr. 12, 69469 Weinheim, Germany

All rights reserved (including those of translation into other languages). No part of this book may be reproduced in any form – by photoprinting, microfilm, or any other means – nor transmitted or translated into a machine language without written permission from the publishers. Registered names, trademarks, etc. used in this book, even when not specifically marked as such, are not to be considered unprotected by law.

Print ISBN:978‐3‐527‐34754‐4

ePDF ISBN:978‐3‐527‐82685‐8

ePub ISBN:978‐3‐527‐82686‐5

oBook ISBN:978‐3‐527‐82687‐2

Jonathan Baell

(Monash University)

Gabriele Costantino

(University of Parma)

Jagath Reddy Junutula

(ModMab Therapeutics)

Kazumi Kondo

(Otsuka)

Roberto Pellicciari

(TES Pharma S.r.l.)

David Rotella

(Montclair State University)

The International Union of Pure and Applied Chemistry ( IUPAC ) supports the publication of the book series Successful Drug Discovery as projects. In these books, experts and key inventors describe and analyze different aspects of drug discovery.

The fifth volume of Successful Drug Discovery has the same structure as the previous volumes. New drug discoveries will be discussed in three parts: Part I: General Aspects, Part II: Drug Class Studies, and Part III: Case Studies encompassing both small‐molecule drugs and biologics.

The editors thank the advisory board members: Jonathan Baell (Monash University), Gabriele Costantino (University of Parma), Jagath R. Junutula (ModMab Therapeutics), Kazumi Kondo (Otsuka Pharmaceutical), Roberto Pellicciari (TES Pharma), and David Rotella (Montclair State University). Special thanks go to the following reviewers who helped both the authors and the editors: John M. Beals, András Kern, Béla Kiss, Thomas Luebbers, Gerd Schnorrenberg, William N. Washburn, and Peng Wu. Special thanks are due to Juergen Stohner for his review from the viewpoint of the IUPAC Interdivisional Committee on Terminology, Nomenclature, and Symbols (ICTNS).

Oliver Plettenburg (University of Hannover and Helmholtz Centre Munich) affords an overview on drug discoveries originating from academic research. The chapter covers both small‐molecule drugs and biologics as well as some natural product‐derived drugs. The chapter testifies to how drug discovery has become vital and indispensable discipline at many academic institutions.

Ynonne Alice Nagel , Adrian Britschgi , and Antonio Ricci (Roche) summarize new ways of breaking down disease‐associated proteins. Targeted protein degradation via so‐called PROTACS and other approaches now allows researchers to modulate previously undruggable target proteins.

Lars Linderoth, Jacob Kofoed, János T. Kodra, Steffen Reedtz‐Runge , and Thomas Kruse (Novo‐Nordisk) review the very important drug class of GLP‐1R agonists for the treatment of diabetes type 2. Since the discovery of GLP‐1 in the 1980s and the launch of the first GLP‐1R agonist‐based therapeutics, multiple development paths have arisen for this successful class of drugs.

Ana Marta de Matos, Patr cia Calado , William Washburn, and Amélia Pilar Rauter (University of Lisbon) report on another very important drug class for the treatment of diabetes type 2: SGLT2 (sodium‐glucose cotransporter‐2) inhibitors. The pioneer drug dapagliflozin initiated drug research resulting in several new and successful analogues. The chapter focuses on recent synthetic advances and clinical data for this class of drugs.

Whitney Gladney, Julie Jadlowsky , Megan M. Davis, and Andrew Fesnak (University of Pennsylvania) review the field of cell‐based therapy in a chapter on “CAR T Cells: A Novel Biological Drug Class.” Their chapter describes the first cell‐based gene therapy treatment used for the treatment of relapsed acute lymphoblastic leukemia.