Successful Drug Discovery.Vol.2

PART I. HDAC Inhibitor Anticancer Drug Discovery
 
FROM DMSO TO THE ANTICANCER COMPOUND SAHA, AN UNUSUAL INTELLECTUAL PATHWAY FOR DRUG DESIGN
Introduction
The Discovery of SAHA (vorinostat)
Clinical Trials
Follow-On Research - Selective HDAC Inhibitors
Conclusion
 
ROMIDEPSIN AND THE ZINC-BINDING THIOL FAMILY OF NATURAL PRODUCT HDAC INHIBITORS
Histone Deacetylases as a Therapeutic Target
The Discovery and Development of Romidepsin
The Zinc-Binding Thiol Family of Natural Product HDAC Inhibitors
Synthetic Analogues of the Zinc-Binding Thiol Natural Products
Summary
 
THE DISCOVERY AND DEVELOPMENT OF BELINOSTAT
Introduction
Discovery of Belinostat
Belinostat Biological Profiling
Formulation Development
Clinical Development
Conclusions
 
DISCOVERY AND DEVELOPMENT OF FARYDAK (NVP-LBH589, PANOBINOSTAT) AS AN ANTICANCER DRUG
Target Identification: From p21Wafl Induction to HDAC Inhibition
Program Flowchart Assays for Drug Discovery
Hit-To-Lead Campaign: Trichostatin A to LAK974
Lead Optimization: LAK974 to LAQ824
Profiling LAQ824 for Cancer Therapy
Preclinical Development of LAQ824
LAQ824 Follow-Up
Discovery of LBH589
Safety Profile for LBH589
Pan-HDAC Inhibition by LBH589
Cancer Cell-Specific Cytotoxicity of LBH589
 
DISCOVERY AND DEVELOPMENT OF HDAC SUBTYPE SELECTIVE INHIBITOR CHIDAMIDE: POTENTIAL IMMUNOMODULATORY ACTIVITY AGAINST CANCER
Introduction
Discovery of Chidamide
Molecular Mechanisms of Chidamide
Animal Studies
Clinical Development
Future Perspective
 
PART II. Steroidal CYP17 Inhibitor Anticancer Drug Discovery
 
ABIRATERONE ACETATE (ZYTIGA): AN INHIBITOR OF CYP17 AS A THERAPEUTIC FOR CASTRATION-RESISTANT PROSTATE CANCER
Introduction
Discovery and Structure-Activity Relationships (SAR)
Preclinical Characterisation of Abiraterone
Physical Characterisation
Clinical Studies
Conclusion
 
PART III. Anti-Infective Drug Discoveries
 
DISCOVERY OF DELAMANID FOR THE

János Fischer is a Senior Research Scientist at Richter Plc., Budapest, Hungary. He received his MSc and PhD degrees in organic chemistry from the Eotvos University of Budapest under Professor A. Kucsman. Between 1976 and 1978, he was a Humboldt Fellow at the University of Bonn under Professor W. Steglich. He has worked at Richter Plc. since 1981 where he participated in the research and development of leading cardiovascular drugs in Hungary. His main interest is analogue based drug discovery. He is the author of some 100 patents and scientific publications. Since 2014 he is Chair of the Subcommittee on Drug Discovery and Development of IUPAC. He received an honorary professorship at the Technical University of Budapest.
 
Wayne Childers is Associate Professor of Pharmaceutical Sciences at Temple University, Philadelphia, USA. Wayne received his BA (1979) degree from Vanderbilt University in chemistry and PhD (1984) in organic chemistry from the University of Georgia under the direction of Harold Pinnick. He served as an Assistant Adjunct Professor at Bucknell University before accepting a position as a postdoctoral fellow at the Johns Hopkins University School of Medicine in the laboratories of Dr. Cecil Robinson. He then joined Wyeth Research, Inc., working in numerous therapeutic areas, including psychiatric diseases, stroke, and Alzheimer's disease, and the treatment of chronic pain. He stayed with Wyeth for 22 years, before joining the faculty of Temple University in 2010.