Drugs Polypharmacology by In Silico Methods: New Opportunities in Drug Discovery

Risultato della ricerca: Article

6 Citazioni (Scopus)

Abstract

Background: Polypharmacology, defined as the modulation of multiple proteins rather than a single target to achieve a desired therapeutic effect, has been gaining increasing attention since 1990s, when industries had to withdraw several drugs due to their adverse effects, leading to permanent injuries or death, with multi-billiondollar legal damages. Therefore, if up to then the “one drug one target” paradigm had seen many researchers interest focused on the identification of selective drugs, with the strong expectation to avoid adverse drug reactions (ADRs), very recently new research strategies resulted more appealing even as attempts to overcome the decline in productivity of the drug discovery industry. Methods: Polypharmacology consists of two different approaches: the former, concerning a single drug interacting with multiple targets related to only one disease pathway; the latter, foresees a single drug’s action on multiple targets involved in multiple disease pathways. Both new approaches are strictly connected to the discovery of new feasible off targets for approved drugs. Results: In this review, we describe how the in silico facilities can be a crucial support in the design of polypharmacological drug. The traditional computational protocols (ligand based and structure based) can be used in the search and optimization of drugs, by using specific filters to address them against the polypharmacology (fingerprints, similarity, etc.). Moreover, we dedicated a paragraph to biological and chemical databases, due to their crucial role in polypharmacology. Conclusion: Multitarget activities provide the basis for drug repurposing, a slightly different issue of high interest as well, which is mostly applied on a single target involved in more than one diseases. In this contest, computational methods have raised high interest due to the reached power of hardware and software in the manipulation of data.
Lingua originaleEnglish
pagine (da-a)3073-3081
Numero di pagine9
RivistaCURRENT PHARMACEUTICAL DESIGN
Volume22
Stato di pubblicazionePublished - 2016

Fingerprint

Polypharmacology
Drug Discovery
Computer Simulation
Pharmaceutical Preparations
Drug Repositioning
Chemical Databases
Drug Design
Drug Industry
Dermatoglyphics
Therapeutic Uses
Drug-Related Side Effects and Adverse Reactions
Industry
Software
Research Personnel
Ligands

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Drug Discovery

Cita questo

@article{f3cd1189604d47529ad91a718e34a875,
title = "Drugs Polypharmacology by In Silico Methods: New Opportunities in Drug Discovery",
abstract = "Background: Polypharmacology, defined as the modulation of multiple proteins rather than a single target to achieve a desired therapeutic effect, has been gaining increasing attention since 1990s, when industries had to withdraw several drugs due to their adverse effects, leading to permanent injuries or death, with multi-billiondollar legal damages. Therefore, if up to then the “one drug one target” paradigm had seen many researchers interest focused on the identification of selective drugs, with the strong expectation to avoid adverse drug reactions (ADRs), very recently new research strategies resulted more appealing even as attempts to overcome the decline in productivity of the drug discovery industry. Methods: Polypharmacology consists of two different approaches: the former, concerning a single drug interacting with multiple targets related to only one disease pathway; the latter, foresees a single drug’s action on multiple targets involved in multiple disease pathways. Both new approaches are strictly connected to the discovery of new feasible off targets for approved drugs. Results: In this review, we describe how the in silico facilities can be a crucial support in the design of polypharmacological drug. The traditional computational protocols (ligand based and structure based) can be used in the search and optimization of drugs, by using specific filters to address them against the polypharmacology (fingerprints, similarity, etc.). Moreover, we dedicated a paragraph to biological and chemical databases, due to their crucial role in polypharmacology. Conclusion: Multitarget activities provide the basis for drug repurposing, a slightly different issue of high interest as well, which is mostly applied on a single target involved in more than one diseases. In this contest, computational methods have raised high interest due to the reached power of hardware and software in the manipulation of data.",
author = "Ugo Perricone and Riccardo Bonsignore and Antonino Lauria and Roberta Bartolotta and Annamaria Martorana and Carla Gentile",
year = "2016",
language = "English",
volume = "22",
pages = "3073--3081",
journal = "CURRENT PHARMACEUTICAL DESIGN",
issn = "1381-6128",

}

TY - JOUR

T1 - Drugs Polypharmacology by In Silico Methods: New Opportunities in Drug Discovery

AU - Perricone, Ugo

AU - Bonsignore, Riccardo

AU - Lauria, Antonino

AU - Bartolotta, Roberta

AU - Martorana, Annamaria

AU - Gentile, Carla

PY - 2016

Y1 - 2016

N2 - Background: Polypharmacology, defined as the modulation of multiple proteins rather than a single target to achieve a desired therapeutic effect, has been gaining increasing attention since 1990s, when industries had to withdraw several drugs due to their adverse effects, leading to permanent injuries or death, with multi-billiondollar legal damages. Therefore, if up to then the “one drug one target” paradigm had seen many researchers interest focused on the identification of selective drugs, with the strong expectation to avoid adverse drug reactions (ADRs), very recently new research strategies resulted more appealing even as attempts to overcome the decline in productivity of the drug discovery industry. Methods: Polypharmacology consists of two different approaches: the former, concerning a single drug interacting with multiple targets related to only one disease pathway; the latter, foresees a single drug’s action on multiple targets involved in multiple disease pathways. Both new approaches are strictly connected to the discovery of new feasible off targets for approved drugs. Results: In this review, we describe how the in silico facilities can be a crucial support in the design of polypharmacological drug. The traditional computational protocols (ligand based and structure based) can be used in the search and optimization of drugs, by using specific filters to address them against the polypharmacology (fingerprints, similarity, etc.). Moreover, we dedicated a paragraph to biological and chemical databases, due to their crucial role in polypharmacology. Conclusion: Multitarget activities provide the basis for drug repurposing, a slightly different issue of high interest as well, which is mostly applied on a single target involved in more than one diseases. In this contest, computational methods have raised high interest due to the reached power of hardware and software in the manipulation of data.

AB - Background: Polypharmacology, defined as the modulation of multiple proteins rather than a single target to achieve a desired therapeutic effect, has been gaining increasing attention since 1990s, when industries had to withdraw several drugs due to their adverse effects, leading to permanent injuries or death, with multi-billiondollar legal damages. Therefore, if up to then the “one drug one target” paradigm had seen many researchers interest focused on the identification of selective drugs, with the strong expectation to avoid adverse drug reactions (ADRs), very recently new research strategies resulted more appealing even as attempts to overcome the decline in productivity of the drug discovery industry. Methods: Polypharmacology consists of two different approaches: the former, concerning a single drug interacting with multiple targets related to only one disease pathway; the latter, foresees a single drug’s action on multiple targets involved in multiple disease pathways. Both new approaches are strictly connected to the discovery of new feasible off targets for approved drugs. Results: In this review, we describe how the in silico facilities can be a crucial support in the design of polypharmacological drug. The traditional computational protocols (ligand based and structure based) can be used in the search and optimization of drugs, by using specific filters to address them against the polypharmacology (fingerprints, similarity, etc.). Moreover, we dedicated a paragraph to biological and chemical databases, due to their crucial role in polypharmacology. Conclusion: Multitarget activities provide the basis for drug repurposing, a slightly different issue of high interest as well, which is mostly applied on a single target involved in more than one diseases. In this contest, computational methods have raised high interest due to the reached power of hardware and software in the manipulation of data.

UR - http://hdl.handle.net/10447/207019

M3 - Article

VL - 22

SP - 3073

EP - 3081

JO - CURRENT PHARMACEUTICAL DESIGN

JF - CURRENT PHARMACEUTICAL DESIGN

SN - 1381-6128

ER -