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After more than fifty years of blockbuster drug development, skeptics are beginning to fear we may be reaching the end of drug discovery to combat major diseases. In this engaging book, Brent Stockwell, a leading researcher in the exciting new science of chemical biology, describes this dilemma and the powerful techniques that may bring drug research into the twenty-first century.
Filled with absorbing stories of breakthroughs, the book begins with the scientific achievements of the twentieth century that led to today's drug innovations. We learn how the invention of mustard gas in World War led to early anti-cancer agents and how the efforts to decode the human genome might lead to new approaches in drug design. Stockwell then turns to the seemingly incurable diseases we face today, such as Alzheimer's, many cancers, and others with no truly effective medicines, and describes cellular and molecular barriers thwarting scientists who use tools from traditional pharmaceutical research.
Scientists such as Stockwell are now developing methods to combat these complexities& mdash;technologies for constructing and testing millions of drug candidates, sophisticated computational modeling, and entirely new classes of drug molecules& mdash;all with an eye toward solving the most profound mysteries of living systems and finding cures for intractable diseases. If successful, these methods will unlock a vast terrain of untapped drug targets that could lead to a bounty of breakthrough medicines. Offering a rare, behind-the-scenes look at this cutting-edge research, The Quest for the Cure tells a thrilling story of science, persistence, and the quest underway to develop a new generation of cures.
— Derek B. Lowe
— Donald C. Lo
— David Kroll
— Garrett A. FitzGerald
List of Illustrations xi
Part 1 The Vanishing Cures
1 The Drug Discovery Crisis 3
2 A New Science of Molecules 24
3 The Birth of the First Cancer Drugs 45
4 A New Company Creating Drug Combinations 66
5 The Undruggable RAS Protein 81
6 The Druggable Genome 101
Part 2 The Path to the Next Generation of Medicines
7 Peering Inside Proteins 119
8 The Nature of Interactions Between Proteins 139
9 From Protein-Protein Interactions to Personalized Medicines 156
10 A Revolution in Peptide Synthesis 169
11 A Vast Array of Drug Candidates 185
12 Moving Outside the Small Molecule Box 205
13 Acceleratingthe Arrival of Next-Generation Drugs 224