Designing Multi-Target Drugs (eBook)

Richard Morphy gained his BSc (1995) and PhD (1989; supervisor: Prof. David Parker) in Chemistry from University of Durham 1989-1995: Medicinal chemist at Celltech, Slough, UK working on oncology and inflammation projects 1995-to date: Section head / Senior Research Fellow at Organon/SPRI/MSD, Newhouse, Scotland working on CNS and CV projects. He has an extensive track record of research, publications and presentations in the area of multi-target drug discovery (MTDD). John Harris gained his BSc.(Chemistry, 1999) from University of Exeter; PhD (Chemistry, 1974) from Queen Mary College, University of London (Supervisor: Prof. B.C.L. Weedon FRS) Postdoc study 1973-1975 with Prof. C.W.Rees at University of Liverpool. 1975 - 1982 Medicinal Chemist at Wellcome Labs, Beckenham, working on cardiovascular projects. 1983-1988 Principal Scientist 1989 - 1995 Head of Cardiovascular Area, Wellcome UK. 1996 - 2008 Founder and CSO of BioFocus (now division of Galapagos); 2009 - to date, independent pharma/biotech consultant. Comprehensive track record of research, publications and presentations in the areas of enzyme inhibitors, prostaglandins, compound library design, kinase drug development in oncology, inflammation and CNS, and multi-targeted drug discovery.

Preface; Forewords; Simple drugs do not cure complex diseases - the need for multi-targeted drugs; Clinical Need and Rationale for Multi-Target Drugs in Psychiatry; Drug molecules and biology: network and systems aspects; Chemoinformatic approaches to target identification; In vitro Panel Screening - Biological Fingerprinting; Phenotypic and in vivo Screening; Lead Discovery and Drug Repurposing; Target/s identification approaches - experimental biological approaches; Historical strategies for lead generation; In silico Lead Generation Approaches in Multi-Target Drug Discovery; The challenges of multi-target lead optimization; Combination agents versus multi-targeted agents - pros and cons; CASE STUDIES: The Discovery of Lapatinib; Identification and optimization of dual PI3K/mTOR inhibitors; Discovery of HDAC-inhibiting multi-target inhibitors; Targeting protein-protein interactions; dual inhibitors of Bcl-2 and Bcl-xL; Discovery of the anti-psychotic drug, Ziprasidone; The Rational Design of Triple Reuptake Inhibitors for the Treatment of Depression; Discovery of multi-target agents for neurological diseases via ligand design; Designing Drugs with Dual Activity: Novel Dual Angiotensin II and Endothelin Receptor Antagonists; Case study 10: Ethyl Urea Inhibitors of the Bacterial Type II Topoisomerases DNA Gyrase (GyrB) and Topoisomerase IV (ParE); Epilogue; Index