Structure-based virtual screening approaches in kinase-directed drug discovery

Dávid Bajusz, G. Ferenczy, György M. Keserű

Research output: Contribution to journalReview article

22 Citations (Scopus)

Abstract

Protein kinases are one of the most targeted protein families in current drug discovery pipelines. They are implicated in many oncological, inflammatory, CNS-related and other clinical indications. Virtual screening is a computational technique with a diverse set of available tools that has been shown many times to provide novel starting points for kinase-directed drug discovery. This review starts with a concise overview of the function, structural features and inhibitory mechanisms of protein kinases. In addition to briefly reviewing the practical aspects of structure-based virtual screenings, we discuss several case studies to illustrate the state of the art in the virtual screening for type I, type II, allosteric (type III-V) and covalent (type VI) kinase inhibitors. With this review, we strive to provide a summary of the latest advances in the structure-based discovery of novel kinase inhibitors, as well as a practical tool to anyone who wishes to embark on such an endeavor.

Original languageEnglish
Pages (from-to)2235-2259
Number of pages25
JournalCurrent Topics in Medicinal Chemistry
Volume17
Issue number20
DOIs
Publication statusPublished - Aug 1 2017

Fingerprint

Drug Discovery
Phosphotransferases
Protein Kinases
Proteins

Keywords

  • Activation segment
  • Covalent docking
  • DFG motif
  • Docking
  • Drug discovery
  • Hinge
  • Inhibitor
  • Kinase
  • Structure-based virtual screening

ASJC Scopus subject areas

  • Drug Discovery

Cite this

Structure-based virtual screening approaches in kinase-directed drug discovery. / Bajusz, Dávid; Ferenczy, G.; Keserű, György M.

In: Current Topics in Medicinal Chemistry, Vol. 17, No. 20, 01.08.2017, p. 2235-2259.

Research output: Contribution to journalReview article

@article{f76ca5c824224dddbc1baeeda2eef398,
title = "Structure-based virtual screening approaches in kinase-directed drug discovery",
abstract = "Protein kinases are one of the most targeted protein families in current drug discovery pipelines. They are implicated in many oncological, inflammatory, CNS-related and other clinical indications. Virtual screening is a computational technique with a diverse set of available tools that has been shown many times to provide novel starting points for kinase-directed drug discovery. This review starts with a concise overview of the function, structural features and inhibitory mechanisms of protein kinases. In addition to briefly reviewing the practical aspects of structure-based virtual screenings, we discuss several case studies to illustrate the state of the art in the virtual screening for type I, type II, allosteric (type III-V) and covalent (type VI) kinase inhibitors. With this review, we strive to provide a summary of the latest advances in the structure-based discovery of novel kinase inhibitors, as well as a practical tool to anyone who wishes to embark on such an endeavor.",
keywords = "Activation segment, Covalent docking, DFG motif, Docking, Drug discovery, Hinge, Inhibitor, Kinase, Structure-based virtual screening",
author = "D{\'a}vid Bajusz and G. Ferenczy and Keserű, {Gy{\"o}rgy M.}",
year = "2017",
month = "8",
day = "1",
doi = "10.2174/1568026617666170224121313",
language = "English",
volume = "17",
pages = "2235--2259",
journal = "Current Topics in Medicinal Chemistry",
issn = "1568-0266",
publisher = "Bentham Science Publishers B.V.",
number = "20",

}

TY - JOUR

T1 - Structure-based virtual screening approaches in kinase-directed drug discovery

AU - Bajusz, Dávid

AU - Ferenczy, G.

AU - Keserű, György M.

PY - 2017/8/1

Y1 - 2017/8/1

N2 - Protein kinases are one of the most targeted protein families in current drug discovery pipelines. They are implicated in many oncological, inflammatory, CNS-related and other clinical indications. Virtual screening is a computational technique with a diverse set of available tools that has been shown many times to provide novel starting points for kinase-directed drug discovery. This review starts with a concise overview of the function, structural features and inhibitory mechanisms of protein kinases. In addition to briefly reviewing the practical aspects of structure-based virtual screenings, we discuss several case studies to illustrate the state of the art in the virtual screening for type I, type II, allosteric (type III-V) and covalent (type VI) kinase inhibitors. With this review, we strive to provide a summary of the latest advances in the structure-based discovery of novel kinase inhibitors, as well as a practical tool to anyone who wishes to embark on such an endeavor.

AB - Protein kinases are one of the most targeted protein families in current drug discovery pipelines. They are implicated in many oncological, inflammatory, CNS-related and other clinical indications. Virtual screening is a computational technique with a diverse set of available tools that has been shown many times to provide novel starting points for kinase-directed drug discovery. This review starts with a concise overview of the function, structural features and inhibitory mechanisms of protein kinases. In addition to briefly reviewing the practical aspects of structure-based virtual screenings, we discuss several case studies to illustrate the state of the art in the virtual screening for type I, type II, allosteric (type III-V) and covalent (type VI) kinase inhibitors. With this review, we strive to provide a summary of the latest advances in the structure-based discovery of novel kinase inhibitors, as well as a practical tool to anyone who wishes to embark on such an endeavor.

KW - Activation segment

KW - Covalent docking

KW - DFG motif

KW - Docking

KW - Drug discovery

KW - Hinge

KW - Inhibitor

KW - Kinase

KW - Structure-based virtual screening

UR - http://www.scopus.com/inward/record.url?scp=85018928693&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85018928693&partnerID=8YFLogxK

U2 - 10.2174/1568026617666170224121313

DO - 10.2174/1568026617666170224121313

M3 - Review article

C2 - 28240180

AN - SCOPUS:85018928693

VL - 17

SP - 2235

EP - 2259

JO - Current Topics in Medicinal Chemistry

JF - Current Topics in Medicinal Chemistry

SN - 1568-0266

IS - 20

ER -