title: Privileged scaffolds in lead generation.
abstract: BACKGROUND
  The term "privileged scaffold" was coined in 1988 and the strategy was to construct high-affinity ligands from core structures that can bind more than one receptor. Since then, the privileged scaffold-based design has evolved from a stand-alone technology to an integral component of various lead generation platforms.
  
  
  METHODS
  In this review, the authors discuss the applications of the privileged scaffold concept in current lead generation. Specifically, the authors cover the role that privileged scaffolds have played in the mass production of compounds to feed high-throughput screening (HTS) and its role in the design of ligands targeting protein-protein interactions, multiple ligands and warhead-based ligands. It is not the intention of the authors to review all privileged scaffolds known to date. Rather, the aim of this review is to highlight the strategic value of the concept of privileged scaffolds in various contemporary lead generation platforms.
  
  
  CONCLUSIONS
  The privileged scaffolds as described by the original definition proved abundant in the available chemical space. HTS and other screening methods, in addition to greatly enhanced compound collections, make privileged scaffold-based design less relevant in finding high-affinity ligands than originally envisioned. However, the principle of privileged scaffolds has greatly enhanced and empowered current lead generation technologies.
authors.affiliation: AbbVie Inc., Research and Development , 1 North Waukegan Road, North Chicago, IL 60064 , USA +1 847 935 4566 ; hongyu.zhao@abbvie.com.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Zhao
authors.forename: Justin
authors.initials: J
authors.lastname: Dietrich
mesh_terms: D015195:Drug Design; D055808:Drug Discovery / Q000379:methods*; D057166:High-Throughput Screening Assays / Q000379:methods*; D006801:Humans; D008024:Ligands; D011485:Protein Binding
chemical_list: D008024:Ligands
keywords: binding warheads; high-throughput screening; multiple ligands; privileged scaffold; protein-protein interactions