Identification of novel inhibitors of extracellular signal-regulated kinase 2 based on the structure-based virtual screening

Hwangseo Park, Young Jae Bahn, Dae Gwin Jeong, Eui Jeon Woo, Jung Sun Kwon, Seong Eon Ryu

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Extracellular signal-regulated kinase 2 (ERK2) has become an attractive target for the development of therapeutics for the treatment of cancer. We have been able to identify eight new inhibitors of ERK2 by means of a drug design protocol involving the virtual screening with docking simulations and in vitro enzyme assay. The newly discovered inhibitors can be categorized into three structural classes and reveal a significant potency with IC50 values ranging from 1 to 30 μM. Therefore, all of the three inhibitor scaffolds deserve further development by structure-activity relationship or de novo design methods. Structural features relevant to the stabilizations of the newly identified inhibitors in the ATP-binding site of ERK2 are discussed in detail.

Original languageEnglish
Pages (from-to)5372-5376
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume18
Issue number20
DOIs
StatePublished - 2008 Oct 15

Fingerprint

Mitogen-Activated Protein Kinase 1
Screening
Drug Design
Enzyme Assays
Structure-Activity Relationship
Scaffolds
Inhibitory Concentration 50
Assays
Stabilization
Adenosine Triphosphate
Binding Sites
Enzymes
Pharmaceutical Preparations
Neoplasms
Therapeutics

Keywords

  • Anticancer agents
  • Docking
  • ERK2
  • Inhibitor
  • Virtual screening

Cite this

Park, Hwangseo ; Bahn, Young Jae ; Jeong, Dae Gwin ; Woo, Eui Jeon ; Kwon, Jung Sun ; Ryu, Seong Eon. / Identification of novel inhibitors of extracellular signal-regulated kinase 2 based on the structure-based virtual screening. In: Bioorganic and Medicinal Chemistry Letters. 2008 ; Vol. 18, No. 20. pp. 5372-5376.
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Identification of novel inhibitors of extracellular signal-regulated kinase 2 based on the structure-based virtual screening. / Park, Hwangseo; Bahn, Young Jae; Jeong, Dae Gwin; Woo, Eui Jeon; Kwon, Jung Sun; Ryu, Seong Eon.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 18, No. 20, 15.10.2008, p. 5372-5376.

Research output: Contribution to journalArticle

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