Clinical candidates modulating protein-protein interactions: the fragment-based experience

Dario Valenti, Stanimira Hristeva, Dimitrios Tzalis (Corresponding author), Christian Ottmann (Corresponding author)

Research output: Contribution to journalReview articlepeer-review

19 Citations (SciVal)
1 Downloads (Pure)


Protein-protein interactions (PPIs) cover a very wide range of biological functions and consequently have become one of the favourite targets for new therapeutic strategies. PPIs are strongly characterised by an intricate and dynamic network of surface interactions occurring between two or more proteins. Because of the complexity of these interactions, many strategies have been applied with the aim to find selective modulators for a specific protein-protein complex. During the last decade, fragment-based approaches have served many drug discovery programs with an impressive increment of contributions, gaining a remarkable role in PPIs modulators’ development. In this review, we detail the successful fragment-to-clinical candidate evolutions related to PPI modulation. An overview on the physico-chemical properties of both fragment hits and lead compounds will be presented together with a statistical analysis of their distribution.

Original languageEnglish
Pages (from-to)76-95
Number of pages20
JournalEuropean Journal of Medicinal Chemistry
Publication statusPublished - 1 Apr 2019


  • Clinical candidate
  • Fragment-based
  • Modulator
  • Protein-protein interaction
  • Drug Discovery/methods
  • Animals
  • Multiprotein Complexes/drug effects
  • Humans
  • Peptide Fragments/chemistry
  • Protein Interaction Domains and Motifs/drug effects
  • Protein Interaction Maps


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