Discovery of Inhibitors of Protein-Protein Interactions from Combinatorial Libraries

Vicent, Marı́a J.; Pérez‐Payá, Enrique; Orzáez, Mar

doi:10.2174/156802607779318307

Cited by 13 publications

(9 citation statements)

References 127 publications

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“…[91] A cyclic derivative (cyclic derivative 2 in reference [92], now named SVT016426) showed improved cell internalization and anti-apoptotic activity in a broad panel of cell lines. [90,92,93] In the same way the fusion of the original peptoid-1 to a polymeric carrier (PGA-1) facilitated cell delivery and improved the activity of the compound in cellular assays. Moreover, PGA-1 showed anti-apoptotic activity in primary cultures of cardiomyocytes subjected to hypoxic conditions.…”

Section: Modulation Of Apoptosomementioning

confidence: 99%

Peptides and Peptide Mimics as Modulators of Apoptotic Pathways

et al. 2009

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Programmed cell death is an important and stringently controlled process. Aberrancies in its control mechanisms can lead to disease; overactive apoptosis can cause neurodegenerative disorders, whereas deficient apoptotic activity can lead to cancer. Therefore, controlling apoptotic pathways with peptides is showing increasing promise as a strategy in drug development.Programmed cell death or apoptosis is a noninvasive and strictly regulated cellular process required for organism development and tissue homeostasis. Deficiencies in apoptotic pathways are the source of many diseases such as cancer, neurodegenerative and autoimmune diseases, and disorders related to an inappropriate loss of cells such as heart failure, stroke, and liver injury. Validation of the various points of intervention as targets for drug development has been the subject of a vast number of studies. Peptides are essential tools for drug discovery, as well as preclinical and pharmaceutical drug development.

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Section: Modulation Of Apoptosomementioning

confidence: 99%

Peptides and Peptide Mimics as Modulators of Apoptotic Pathways

et al. 2009

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“…Jusqu'à aujourd'hui, les sociétés pharmaceutiques se sont plutôt concentrées sur les inhibiteurs d'activités enzymatiques virales ou sur des molécules interférant avec les récepteurs, donc avec l'entrée virale. Déstabiliser les interactions protéine-protéine entre protéines virales ou protéines virales et cellulaires constitue un concept plus récent qui offre de nombreuses cibles prometteuses [13,14]. Pour interférer avec ces liaisons, les peptides sont d'excellents outils qui, comparés aux molécules utilisées traditionellement, présentent des caractéristiques thérapeutiques trés intéressantes [5].…”

Section: Les Peptides Antiviraux Une Nouvelle Voie Prometteuseunclassified

“…Les approches de « drug discovery » font appel à des techniques permettant de cribler à haut débit (HTS : « high throughput screening ») des banques de composés biologiques naturels ou générés par chimie combinatoire (acides nucléiques, peptides, protéines) de très grande diversité de façon à isoler rapidement des candidats antiviraux [22]. Ces approches sont particulièrement utiles lorsqu'un manque de connaissances concernant la protéine cible rend inapplicables des techniques plus rationnelles [13].…”

Section: Les Approches Combinatoiresunclassified

Nouvelles stratégies pour la conception de molécules antivirales

Castel

Tordo

2009

Revue Francophone des Laboratoires

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“…Classical approaches, such as high-throughput screening of a historical compounds, failed to provide high-affinity compounds [ 29 ], and several other approaches have been developed with only partial success [ 29 , 58 ]. Finally, a dual inhibitor of Bcl-2 and Bcl-X L was discovered by Rosenberg, Fesik and co-workers [ 4 , 59 – 62 ]. The successful strategy was to apply what has since become known as fragment-based drug discovery [ 38 , 41 , 63 , 64 ].…”

Section: Introductionmentioning

confidence: 99%

“…For this reason, current libraries are focussed on maximizing the molecular complexity and diversity rather than complying with the rule of five [ 25 , 26 , 38 , 41 , 42 ]. These new libraries of natural and synthetic compounds have demonstrably been a more efficient approach for the discovery of small molecules capable of interference with PPI motifs [ 3 , 43 , 60 – 62 , 108 , 109 ]. Recently, a library of 10,000 compounds was screened for potential inhibitors of Min1-PDZ (involved in the synaptic function and target to treat pain) identifying several lead molecules [ 110 ].…”

Section: Introductionmentioning

confidence: 99%

Motif mediated protein-protein interactions as drug targets

Corbi‐Verge

Kim

2016

Cell Commun Signal

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Protein-protein interactions (PPI) are involved in virtually every cellular process and thus represent an attractive target for therapeutic interventions. A significant number of protein interactions are frequently formed between globular domains and short linear peptide motifs (DMI). Targeting these DMIs has proven challenging and classical approaches to inhibiting such interactions with small molecules have had limited success. However, recent new approaches have led to the discovery of potent inhibitors, some of them, such as Obatoclax, ABT-199, AEG-40826 and SAH-p53-8 are likely to become approved drugs. These novel inhibitors belong to a wide range of different molecule classes, ranging from small molecules to peptidomimetics and biologicals. This article reviews the main reasons for limited success in targeting PPIs, discusses how successful approaches overcome these obstacles to discovery promising inhibitors for human protein double minute 2 (HDM2), B-cell lymphoma 2 (Bcl-2), X-linked inhibitor of apoptosis protein (XIAP), and provides a summary of the promising approaches currently in development that indicate the future potential of PPI inhibitors in drug discovery.

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Discovery of Inhibitors of Protein-Protein Interactions from Combinatorial Libraries

Cited by 13 publications

References 127 publications

Peptides and Peptide Mimics as Modulators of Apoptotic Pathways

Peptides and Peptide Mimics as Modulators of Apoptotic Pathways

Nouvelles stratégies pour la conception de molécules antivirales

Motif mediated protein-protein interactions as drug targets

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