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 language | English |
|---|---|
| Pages (from-to) | 5372-5376 |
| Number of pages | 5 |
| Journal | Bioorganic and Medicinal Chemistry Letters |
| Volume | 18 |
| Issue number | 20 |
| DOIs | |
| State | Published - 2008 Oct 15 |
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Keywords
- Anticancer agents
- Docking
- ERK2
- Inhibitor
- Virtual screening
Cite this
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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 journal › Article
TY - JOUR
T1 - Identification of novel inhibitors of extracellular signal-regulated kinase 2 based on the structure-based virtual screening
AU - Park, Hwangseo
AU - Bahn, Young Jae
AU - Jeong, Dae Gwin
AU - Woo, Eui Jeon
AU - Kwon, Jung Sun
AU - Ryu, Seong Eon
PY - 2008/10/15
Y1 - 2008/10/15
N2 - 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.
AB - 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.
KW - Anticancer agents
KW - Docking
KW - ERK2
KW - Inhibitor
KW - Virtual screening
UR - http://www.scopus.com/inward/record.url?scp=53349102835&partnerID=8YFLogxK
U2 - 10.1016/j.bmcl.2008.09.058
DO - 10.1016/j.bmcl.2008.09.058
M3 - Article
C2 - 18835158
AN - SCOPUS:53349102835
VL - 18
SP - 5372
EP - 5376
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
SN - 0960-894X
IS - 20
ER -