EARLY DRUG DEVELOPMENT: BRINGING A PRECLINICAL CANDIDATE TO THE CLINIC

Contents to Volume 1
1 Early Drug Development: Progressing a Candidate Compound to the Clinics 1
• Part I Drug Substance 9
2 Early Phase API Process Development Overview 11
3 The Discovery/Development Transition 31
4 Active Pharmaceutical Ingredient Cost of Goods: Discovery to Early Development 49
5 New Technologies in Process Development 73
6 Vortioxetine and Early Drug Development Considerations at the Interface of R&D 125
7 Development of a Practical Synthesis of 4'-Azido-2 Methyl-2'-Desoxycytosine and Its Prodrugs as HCV Chemotherapeutic Agents 145
• Part II Drug Product 169
8 Solubility, Permeability, and Their Interplay 171
9 Solid-State Properties 203
10 Salt and Cocrystal Screening 229
11 Particle Size Reduction: From Microsizing to Nanosizing 271
12 Early Drug Development: From a Drug Candidate to the Clinic 305
13 A Practical Guide for the Preparation of Drug Nanosuspensions for Preclinical Studies: Including In Vivo Case Studies 333
Contents to Volume 2
• Part III Pharmacokinetics and Pharmacodynamics 365
14 Integration of Pharmacokinetic and Pharmacodynamic Reasoning and Its Importance in Drug Discovery 367
15 Prediction of Human Pharmacokinetics and Pharmacodynamics 399
16 Translational Modeling and Simulation for Molecularly Targeted Small Molecule Anticancer Agents: Case Studies of Multiple Tyrosine Kinase Inhibitors, Crizotinib and Lorlatinib 433
17 Informing Decisions in Discovery and Early Development Research Through Quantitative and Translational Modeling 467
• Part IV Toxicology 497
18 Preclinical Toxicology Evaluation 499
19 Nonclinical Safety Pharmacology 527
20 Early Drug Development 549
21 Addressing Genotoxicity Risk in Lead Optimization: A PDE10A Inhibitor Case Study 581
22 The Integrated Optimization of Safety and DMPK Properties Enabling Preclinical Development: A Case History with S1P1 Agonists 603
23 From TRAIL to ONC201: Case Study on the Safety Benefit of Developing Targeted Agents Against Cancer-selective Pathways 631
• Part V Intellectural Property 647
24 Patent Law Relevant to Early Drug Development 649
25 Patent Protection Strategy 667
26 Intellectual Property: The Patent Landscape Viewed from Generic and Originator Perspectives 691
27 Patent Considerations in Collaborative Drug Development 721

Index 749

This one-stop reference systematically covers key aspects in early drug development that are directly relevant to the discovery phase and are required for first-in-human studies.
Its broad scope brings together critical knowledge from many disciplines, ranging from process technology to pharmacology to intellectual property issues.
After introducing the overall early development workflow, the critical steps of early drug development are described in a sequential and enabling order: the availability of the drug substance and that of the drug product, the prediction of pharmacokinetics and -dynamics, as well as that of drug safety. The final section focuses on intellectual property aspects during early clinical development. The emphasis throughout is on recent case studies to exemplify salient points, resulting in an abundance of practice-oriented information that is usually not available from other sources.
Aimed at medicinal chemists in industry as well as academia, this invaluable reference enables readers to understand and navigate the challenges in developing clinical candidate molecules that can be successfully used in phase one clinical trials.