Cover Page

Successful Drug Discovery

Volume 3


Edited by J´nos Fischer, Christian Klein andWayne E. Childers

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Advisory Board Members

Magid Abou-Gharbia(Temple University, USA) Anette Graven-Sams(Lundbeck, Denmark)
Kazumi Kondo(Otsuka, Japan) John A. Lowe(JL3Pharma LLC, USA)
Barry V.L. Potter(Oxford University, UK) Gerd Schnorrenberg(Boeringer Ingelheim, Germany)


The third volume of Successful Drug Discovery has a structural similarity to the first volume consisting of three parts: General Aspects, Drug Class Studies, and Case Histories. The book series supported by the International Union of Pure and Applied Chemistry (IUPAC) focuses on new drug discoveries. This volume investigates drug discoveries of the last years, that is, small-molecule drugs and biologics approved between 2013 and 2016. The book therefore contains both medicinal chemistry and biological drug research with a concept to bring these two disciplines closer to each other.

The editors thank the advisory board members – Kazumi Kondo (Otsuka, Japan) and Barry V.L. Potter (Oxford University, UK) – and the following reviewers who helped both the authors and the editors: Jim Barrow, Mark S. Cragg, Doriano Fabbro, Duke Fitch, Burkhard Fugmann, Jagath Reddy Junutula, Béla Kiss, Paul Leeson, John McCall, Carlo De Micheli, Jens-Uwe Peters, John Proudfoot, Chack Ramesha, Mathias Rask-Andersen, Jörg Senn-Bilfinger, Steve Staben, Ronald P. Taylor, Klaus T. Wanner, Scott Wolkenberg, Jay Wrobel, and Takayuki Yoshino. Special thanks are due to Ron Weir for his review from the viewpoints of the IUPAC Interdivisional Committee on Terminology, Nomenclature and Symbols (ICTNS).

Part I: General Aspects

Gerd Schnorrenberg gives an overview in the introductory chapter “New Trends in Drug Discovery” on the changing status of new drug discoveries in which besides small-molecule drugs, an increasing role of biopharmaceutical drugs can be observed.

Ulrich Storz and coworkers summarize important information in their chapter “Patenting Small and Large Pharmaceutical Molecules”, which are useful for all participants of drug research, both in academia and industry.

Part II: Drug Class Studies

Peng Wu and coworker reviewed all approved “Kinase Inhibitor Drugs” whose number amounted to 38 when this article was prepared, and they represent one of the most successful fields of drug discoveries.

Arwed Clewe and coworker provide a stepwise account on how drug discoveries optimized the drug therapy of prostate cancer in their chapter “Evolution of Non-Steroidal Androgen Receptor Antagonists.”

Part III: Case Studies

  1. 1.


    Patrick A. Baeuerle describes the history, design, and development of blinatumomab, which is a new bispecific T-cell engager monoclonal antibody for the treatment of Philadelphia chromosome-negative adult patients with relapsed/refractory acute lymphoblastic leukemia.

  2. 2.


    Pierre-Yves Michellys reports on the discovery and development of ceritinib, a new inhibitor of anaplastic lymphoma kinase (ALK) for the treatment of ALK-positive metastatic non-small cell lung cancer.

  3. 3.


    Maarten L. Janmaat and coworkers have written a chapter on the discovery and development of daratumumab, which is a new monoclonal antibody for the treatment of multiple myeloma.

  4. 4.

    Obeticholic acid

    Roberto Pellicciari and coworkers describe how obeticholic acid, the first-in-class farnesoid X receptor (FXR) agonist, was discovered to afford a new drug for the treatment of primary biliary cholangitis. It is a good example for a successful cooperation of academia and industry in drug research.

  5. 5.


    Christian Klein and coworkers have written a chapter on the discovery and development of the type II CD20 monoclonal antibody obinutuzumab, which has been approved by Food and Drug Administration (FDA) for the treatment of chronic lymphocytic leukemia.

  6. 6.


    Tesfaye Biftu has given an overview on how the long-lasting DPP-4 inhibitor omarigliptin was discovered for the once-weekly treatment of type 2 diabetes.

  7. 7.


    László Kiss and coworkers describe the discovery and development of the very long-acting catechol-O-methyltransferase (COMT) inhibitor opicapone, which is approved by the European Medicines Agency (EMA) as adjunctive therapy for Parkinson's disease.

  8. 8.


    Michael J. Waring reports on a third-generation EGFR inhibitor osimertinib for the treatment of advanced non-small cell lung cancer.

  9. 9.


    C. Robin Ganellin and coworkers describe the history how they discovered and developed pitolisant, the first histamine H3-receptor inverse agonist for the treatment of narcolepsy.

  10. 10.


    Mario Varasi and coworker have written a chapter on safinamide, which was approved as an add-on therapy to L-dopa for the treatment of Parkinson's disease.

  11. 11.


    Teiji Takechi and coworkers report on the discovery and development of a new antimetabolite combination drug, in which tipiracil prevents rapid metabolism of the nucleoside analogue.

The editors and authors thank Wiley-VCH and personally Dr. Frank Weinreich for the fruitful cooperation.

János Fischer

Wayne E. Childers

Christian Klein

24 March 2017




Part I
General Philosophy