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Preface

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).

Part I: General Aspects

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.

Part II: Drug Class Studies

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, Patrcia 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.

Sarah Walter and Marcelo E. Bigal (Antiva Biosciences and Ventus Therapeutics) describe CGRP (calcitonin gene‐related peptide) inhibitors for the treatment of migraine, which represent a new class of drugs consisting of both small‐molecule drugs and biologics.

Part III: Case Studies

Takehisa Kitazawa, Koichiro Yoneyama, and Tomoyuki Igawa (Chugai Pharmaceuticals) provide a case study of emicizumab, a humanized bispecific antibody to coagulation factors IXa and X that also possesses factor VIII cofactor activity. Emicizumab (HEMLIBRA™) was approved by US FDA in 2017 for treatment of hemophilia A.

Zenon D. Konteatis and Zhihua Sui (Agios Pharmaceuticals) describe the discovery and development of ivosidenib (Tibsovo™), which was approved by US FDA in 2019 for newly diagnosed acute myeloid leukemia with a susceptible IDH1 mutation.

Christopher T. Brain, Rajiv Chopra, Sunkyu Kim, Steven Howard, and Moo Je Sung (Novartis) recount the discovery of ribociclib (Kisqali™), a CDK4/6 inhibitor for the treatment of HR positive/HER2 negative advanced brain cancer. Ribociclib was approved by the US FDA in 2017 for use in combination with an aromatase inhibitor.

The editors and authors thank Wiley‐VCH and personally Dr. Frank Weinreich and Katherine Wong for the excellent collaboration.

János Fischer

Budapest

Wayne E. Childers

Philadelphia

Christian Klein

Zürich

June 2020