Brent R. Stockwell
- Published in print:
- 2013
- Published Online:
- November 2015
- ISBN:
- 9780231152136
- eISBN:
- 9780231525527
- Item type:
- chapter
- Publisher:
- Columbia University Press
- DOI:
- 10.7312/columbia/9780231152136.003.0011
- Subject:
- Public Health and Epidemiology, Public Health
This chapter examines how the invention of solid-phase peptide synthesis and the birth of combinatorial chemistry have made it possible to screen and allow for the collection of massive amounts of ...
More
This chapter examines how the invention of solid-phase peptide synthesis and the birth of combinatorial chemistry have made it possible to screen and allow for the collection of massive amounts of small molecules as potential drug candidates. Research on the kinds of molecules that should be constructed using solid-phase synthesis and combinatorial chemistry can be traced to Croatia in 1907, when Leo Sternbach successfully obtained a new class of compounds called 1,4-benzodiazepine. Sternbach and his colleagues would later create an even more potent, stable, and effective compound that was introduced in 1963 under the name Valium (diazepam). Between 1965 and 1977, additional benzodiazepines were introduced into the marketplace. In 1986 Ben Evans and his colleagues at Merck Sharp and Dohme Research Laboratories discovered cholecystokinen, a peptide hormine that could block a crucial protein-protein interaction involved in the formation of ulcers and gastrointestinal cancers. This chapter also looks at the studies carried out by Jonathan Ellman and others that led to the creation of large combinatorial libraries for drug discovery.Less
This chapter examines how the invention of solid-phase peptide synthesis and the birth of combinatorial chemistry have made it possible to screen and allow for the collection of massive amounts of small molecules as potential drug candidates. Research on the kinds of molecules that should be constructed using solid-phase synthesis and combinatorial chemistry can be traced to Croatia in 1907, when Leo Sternbach successfully obtained a new class of compounds called 1,4-benzodiazepine. Sternbach and his colleagues would later create an even more potent, stable, and effective compound that was introduced in 1963 under the name Valium (diazepam). Between 1965 and 1977, additional benzodiazepines were introduced into the marketplace. In 1986 Ben Evans and his colleagues at Merck Sharp and Dohme Research Laboratories discovered cholecystokinen, a peptide hormine that could block a crucial protein-protein interaction involved in the formation of ulcers and gastrointestinal cancers. This chapter also looks at the studies carried out by Jonathan Ellman and others that led to the creation of large combinatorial libraries for drug discovery.
Brent Stockwell
- Published in print:
- 2013
- Published Online:
- November 2015
- ISBN:
- 9780231152136
- eISBN:
- 9780231525527
- Item type:
- book
- Publisher:
- Columbia University Press
- DOI:
- 10.7312/columbia/9780231152136.001.0001
- Subject:
- Public Health and Epidemiology, Public Health
After more than fifty years of blockbuster drug development, skeptics are beginning to fear we are reaching the end of drug discovery to combat major diseases. This book describes this dilemma and ...
More
After more than fifty years of blockbuster drug development, skeptics are beginning to fear we are reaching the end of drug discovery to combat major diseases. This book describes this dilemma and the powerful techniques that may bring drug research into the twenty-first century. Filled with absorbing stories of breakthroughs, this 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 I led to early anti-cancer agents and how the efforts to decode the human genome might lead to new approaches in drug design. The book then turns to the seemingly incurable diseases we face today, such as Alzheimer’s, many cancers, and others with no truly effective medicines, and details the cellular and molecular barriers thwarting scientists equipped with only the tools of traditional pharmaceutical research. Scientists are now developing methods to combat these complexities—technologies for constructing and testing millions of drug candidates, sophisticated computational modeling, and entirely new classes of drug molecules—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.Less
After more than fifty years of blockbuster drug development, skeptics are beginning to fear we are reaching the end of drug discovery to combat major diseases. This book describes this dilemma and the powerful techniques that may bring drug research into the twenty-first century. Filled with absorbing stories of breakthroughs, this 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 I led to early anti-cancer agents and how the efforts to decode the human genome might lead to new approaches in drug design. The book then turns to the seemingly incurable diseases we face today, such as Alzheimer’s, many cancers, and others with no truly effective medicines, and details the cellular and molecular barriers thwarting scientists equipped with only the tools of traditional pharmaceutical research. Scientists are now developing methods to combat these complexities—technologies for constructing and testing millions of drug candidates, sophisticated computational modeling, and entirely new classes of drug molecules—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.
