Fragment-based drug design

Strategic advances and lessons learned

H. Chen, X. Zhou, Y. Gao, H. Chen, Jia Zhou

Research output: Chapter in Book/Report/Conference proceedingChapter

1 Citation (Scopus)

Abstract

Over the past two decades, high-throughput screening (HTS) has played a vital role in discovering new chemical leads. Due to the inherent defects and limitations associated with HTS, there exist high attrition rates. Fragment-based drug discovery (FBDD) has emerged as an efficient method to construct leads from weak-affinity fragments, which involves detecting weak fragment-target protein interactions using fragment-based screening (FBS) approaches. In this article, we discuss various FBS assays, compare their advantages and disadvantages, and stress the core principle of orthogonal validation and lead generation. The strategic advances in FBDD and lessons learned from success cases are also presented.

Original languageEnglish (US)
Title of host publicationDrug Discovery Technologies
PublisherElsevier Inc.
Pages212-232
Number of pages21
Volume2-8
ISBN (Electronic)9780128032008
ISBN (Print)9780128032015
DOIs
StatePublished - Jun 3 2017
Externally publishedYes

Fingerprint

Screening
Pharmaceutical Preparations
Throughput
Assays
Defects
Proteins
Drug Discovery

Keywords

  • Drug discovery
  • Fragment evolution
  • Fragment optimization
  • Fragment self-assembly
  • Fragment-based drug design
  • Fragment-based drug discovery
  • Fragment-based screening
  • Fragments
  • High-throughput screening
  • Ligand efficiency
  • Ligand-target interactions
  • Rational drug design
  • Structure-based drug design
  • Therapeutic agents

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

Chen, H., Zhou, X., Gao, Y., Chen, H., & Zhou, J. (2017). Fragment-based drug design: Strategic advances and lessons learned. In Drug Discovery Technologies (Vol. 2-8, pp. 212-232). Elsevier Inc.. https://doi.org/10.1016/B978-0-12-409547-2.12319-4

Fragment-based drug design : Strategic advances and lessons learned. / Chen, H.; Zhou, X.; Gao, Y.; Chen, H.; Zhou, Jia.

Drug Discovery Technologies. Vol. 2-8 Elsevier Inc., 2017. p. 212-232.

Research output: Chapter in Book/Report/Conference proceedingChapter

Chen, H, Zhou, X, Gao, Y, Chen, H & Zhou, J 2017, Fragment-based drug design: Strategic advances and lessons learned. in Drug Discovery Technologies. vol. 2-8, Elsevier Inc., pp. 212-232. https://doi.org/10.1016/B978-0-12-409547-2.12319-4
Chen H, Zhou X, Gao Y, Chen H, Zhou J. Fragment-based drug design: Strategic advances and lessons learned. In Drug Discovery Technologies. Vol. 2-8. Elsevier Inc. 2017. p. 212-232 https://doi.org/10.1016/B978-0-12-409547-2.12319-4
Chen, H. ; Zhou, X. ; Gao, Y. ; Chen, H. ; Zhou, Jia. / Fragment-based drug design : Strategic advances and lessons learned. Drug Discovery Technologies. Vol. 2-8 Elsevier Inc., 2017. pp. 212-232
@inbook{874bbbdfc61b4006ba85eb249ee77a40,
title = "Fragment-based drug design: Strategic advances and lessons learned",
abstract = "Over the past two decades, high-throughput screening (HTS) has played a vital role in discovering new chemical leads. Due to the inherent defects and limitations associated with HTS, there exist high attrition rates. Fragment-based drug discovery (FBDD) has emerged as an efficient method to construct leads from weak-affinity fragments, which involves detecting weak fragment-target protein interactions using fragment-based screening (FBS) approaches. In this article, we discuss various FBS assays, compare their advantages and disadvantages, and stress the core principle of orthogonal validation and lead generation. The strategic advances in FBDD and lessons learned from success cases are also presented.",
keywords = "Drug discovery, Fragment evolution, Fragment optimization, Fragment self-assembly, Fragment-based drug design, Fragment-based drug discovery, Fragment-based screening, Fragments, High-throughput screening, Ligand efficiency, Ligand-target interactions, Rational drug design, Structure-based drug design, Therapeutic agents",
author = "H. Chen and X. Zhou and Y. Gao and H. Chen and Jia Zhou",
year = "2017",
month = "6",
day = "3",
doi = "10.1016/B978-0-12-409547-2.12319-4",
language = "English (US)",
isbn = "9780128032015",
volume = "2-8",
pages = "212--232",
booktitle = "Drug Discovery Technologies",
publisher = "Elsevier Inc.",

}

TY - CHAP

T1 - Fragment-based drug design

T2 - Strategic advances and lessons learned

AU - Chen, H.

AU - Zhou, X.

AU - Gao, Y.

AU - Chen, H.

AU - Zhou, Jia

PY - 2017/6/3

Y1 - 2017/6/3

N2 - Over the past two decades, high-throughput screening (HTS) has played a vital role in discovering new chemical leads. Due to the inherent defects and limitations associated with HTS, there exist high attrition rates. Fragment-based drug discovery (FBDD) has emerged as an efficient method to construct leads from weak-affinity fragments, which involves detecting weak fragment-target protein interactions using fragment-based screening (FBS) approaches. In this article, we discuss various FBS assays, compare their advantages and disadvantages, and stress the core principle of orthogonal validation and lead generation. The strategic advances in FBDD and lessons learned from success cases are also presented.

AB - Over the past two decades, high-throughput screening (HTS) has played a vital role in discovering new chemical leads. Due to the inherent defects and limitations associated with HTS, there exist high attrition rates. Fragment-based drug discovery (FBDD) has emerged as an efficient method to construct leads from weak-affinity fragments, which involves detecting weak fragment-target protein interactions using fragment-based screening (FBS) approaches. In this article, we discuss various FBS assays, compare their advantages and disadvantages, and stress the core principle of orthogonal validation and lead generation. The strategic advances in FBDD and lessons learned from success cases are also presented.

KW - Drug discovery

KW - Fragment evolution

KW - Fragment optimization

KW - Fragment self-assembly

KW - Fragment-based drug design

KW - Fragment-based drug discovery

KW - Fragment-based screening

KW - Fragments

KW - High-throughput screening

KW - Ligand efficiency

KW - Ligand-target interactions

KW - Rational drug design

KW - Structure-based drug design

KW - Therapeutic agents

UR - http://www.scopus.com/inward/record.url?scp=85045048728&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85045048728&partnerID=8YFLogxK

U2 - 10.1016/B978-0-12-409547-2.12319-4

DO - 10.1016/B978-0-12-409547-2.12319-4

M3 - Chapter

SN - 9780128032015

VL - 2-8

SP - 212

EP - 232

BT - Drug Discovery Technologies

PB - Elsevier Inc.

ER -