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 articleAcademicpeer-review

1 Citation (Scopus)

Abstract

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.

LanguageEnglish
Pages76-95
Number of pages20
JournalEuropean Journal of Medicinal Chemistry
Volume167
DOIs
StatePublished - 1 Apr 2019

Fingerprint

Proteins
Modulators
Lead compounds
Drug Discovery
Chemical properties
Statistical methods
Modulation
Therapeutics

Keywords

  • Clinical candidate
  • Fragment-based
  • Modulator
  • Protein-protein interaction

Cite this

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Clinical candidates modulating protein-protein interactions : the fragment-based experience. / Valenti, Dario; Hristeva, Stanimira; Tzalis, Dimitrios (Corresponding author); Ottmann, Christian (Corresponding author).

In: European Journal of Medicinal Chemistry, Vol. 167, 01.04.2019, p. 76-95.

Research output: Contribution to journalReview articleAcademicpeer-review

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