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

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

Onderzoeksoutput: Bijdrage aan tijdschriftArtikel recenserenAcademicpeer review

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Uittreksel

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.

Originele taal-2Engels
Pagina's (van-tot)76-95
Aantal pagina's20
TijdschriftEuropean Journal of Medicinal Chemistry
Volume167
DOI's
StatusGepubliceerd - 1 apr 2019

Vingerafdruk

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

Citeer dit

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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.",
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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, blz. 76-95.

Onderzoeksoutput: Bijdrage aan tijdschriftArtikel recenserenAcademicpeer review

TY - JOUR

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T2 - the fragment-based experience

AU - Valenti, Dario

AU - Hristeva, Stanimira

AU - Tzalis, Dimitrios

AU - Ottmann, Christian

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AB - 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.

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KW - Multiprotein Complexes/drug effects

KW - Humans

KW - Peptide Fragments/chemistry

KW - Protein Interaction Domains and Motifs/drug effects

KW - Protein Interaction Maps

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