RNA as a Drug Target

Provides the concepts and tools for developing drug-like small molecules that selectively target RNA rather than proteins, including the first successful examples from the development pipeline of big pharma.

Auteur

John Schneekloth received his undergraduate degree from Dartmouth College in 2001 where he worked with Prof. Gordon Gribble. He then moved to Yale University and obtained a Ph.D. from the chemistry department with Prof. Craig Crews in 2006. As a graduate student he studied natural product total synthesis and developed the first cell-permeable PROTAC molecules. He then pursued an NIH postdoctoral fellowship with Prof. Erik Sorensen at Princeton University where he worked on the development of a new multicomponent reaction and the application of this reaction to the synthesis of analgesic natural products. He returned to Yale in 2009 where he worked as a medicinal chemist at the Yale Small Molecule Discovery Center. In 2011, Dr. Schneekloth joined NCI where his research involves using synthetic chemistry and high throughput chemical biology approaches to develop chemical probes of RNA, with a particular emphasis on targeting RNA with druglike small molecules.

Martin Pettersson is a medicinal chemistry / drug discovery leader with 18+ years of industrial experience. He received his undergraduate degree from Indiana University in 1998, working with David R. Williams. After four years working for Pfizer, he then joined the University of Texas at Austin for a Ph.D. in Organic Chemistry with Stephen F. Martin. He continued to work for Pfizer, where he delivered multiple compounds into clinical development. He co-led Pfizer's COVID-19 oral protease inhibitor program from project inception until August 2020, during which time the clinical candidate PF-07321332 (Paxlovid) was designed and synthesized. In 2020, he became senior director Neuroscience/Pain at Grünenthal Group, where he is also a member of the Research Board. His publication record includes more than 70 publications, patents/patent applications, and presentations.

Texte du rabat

Discover a new paradigm in drug discovery that greatly expands the space of addressable drug targets and potential novel drugs Existing paradigms for drug discovery have focused largely on enzymes and other proteins as drug targets. In recent years, however, different varieties of ribonucleic acids have emerged as a viable focus for target-based drug discovery, with the potential to revolutionize the strategy and approach for this essential step in the drug development process. RNA as a Drug Target: The Next Frontier for Medicinal Chemistry offers a practice-oriented introduction to developing drug-like small molecules that selectively modulate both coding and non-coding RNAs. Beginning with a description and characterization of existing druggable RNAs, the book discusses how to approach different RNA targets for drug discovery. The result is a crucial resource for targeting RNAs and creating the next generation of life-saving pharmaceuticals. RNA as a Drug Target readers will also find:

• A complete "toolbox" for working with RNA, from structure determination to screening and lead generation techniques
• A wide range of addressable targets and mechanisms, including splicing modulation, riboswitches, targeted degradation, and more
• Authoritative discussion of the potential of RNA-targeted small molecule therapeutics for drugging the epitranscriptome RNA as a Drug Target provides an expert introduction to a new frontier in pharmaceutical research for medicinal chemists, biochemists, molecular biologists, and members of the pharmaceutical industry.

Contenu

1. Introduction
   
   2. RNA Structure Probing, Dynamics, and Folding
   3. High Resolution Structures of RNA
   4. Screening and Lead Generation Techniques for RNA Binders
   5. Chemical Matter that Binds RNA
   6. MicroRNAs as Targets for Small Molecule Binders
   7. Pre-mRNA Splicing Modulation
   8. Prospects for Riboswitches in Drug Development
   9. Small Molecules That Degrade RNA
   10. Approaches to the Identification of Molecules Altering Programmed Ribosomal Frameshifting in Viruses
   11. RNA-Protein Interactions: A New Approach for Drugging RNA Biology
   12. Drugging the Epitranscriptome
   13. Outlook. A Perspective on RNA: The Next Frontier for Small Molecule Therapeutics