Identification and validation of protein targets of bioactive small molecules

Denis V. Titov, Jun O. Liu

Research output: Contribution to journalArticlepeer-review

27 Scopus citations


Identification and validation of protein targets of bioactive small molecules is an important problem in chemical biology and drug discovery. Currently, no single method is satisfactory for this task. Here, we provide an overview of common methods for target identification and validation that historically were most successful. We have classified for the first time the existing methods into two distinct and complementary types, the 'top-down' and 'bottom-up' approaches. In a typical top-down approach, the cellular phenotype is used as a starting point and the molecular target is approached through systematic narrowing down of possibilities by taking advantage of the detailed existing knowledge of cellular pathways and processes. In contrast, the bottom-up approach entails the direct detection and identification of the molecular targets using affinity-based or genetic methods. A special emphasis is placed on target validation, including correlation analysis and genetic methods, as this area is often ignored despite its importance.

Original languageEnglish (US)
Pages (from-to)1902-1909
Number of pages8
JournalBioorganic and Medicinal Chemistry
Issue number6
StatePublished - Mar 15 2012


  • Chemical biology
  • Protein targets
  • Small molecules
  • Target identification
  • Target validation

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry


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