Abstract
Glycogen synthase kinase-3 (GSK-3β) has been emerging as a key therapeutic target for type-2 diabetics, Alzheimer's disease, cancer, and chronic inflammation. For the purpose of finding biologically active and novel compounds and providing new idea for drug-design, we performed virtual screening using commercially available database. Three-dimensional common feature pharmacophore model was developed by using HipHop program provided in Catalyst software and it was used as a query for screening database. Recursive partitioning (RP) model was developed as a filtering system, which was able to classify active and inactive compounds. Eventually, a sequential virtual screening procedure (SQSP) was conducted by applying the common feature pharmacophore and RP model in succession to discover novel potent GSK-3β inhibitors. The final 56 hit compounds were carefully selected considering predicted docking mode in crystal structures. Subsequent enzyme assay for human GSK-3β protein confirmed that three compounds of these hit compounds exhibit micromolar inhibitory activity. Here, we report novel hit compounds and their binding mode in the active site of GSK-3β crystal structure.
| Original language | English |
|---|---|
| Pages (from-to) | 636-643 |
| Number of pages | 8 |
| Journal | Bioorganic and Medicinal Chemistry |
| Volume | 16 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 2008 Jan 15 |
Fingerprint
All Science Journal Classification (ASJC) codes
- Biochemistry
- Molecular Medicine
- Molecular Biology
- Pharmaceutical Science
- Drug Discovery
- Clinical Biochemistry
- Organic Chemistry
Cite this
}
Novel GSK-3β inhibitors from sequential virtual screening. / Kim, Hye Jung; Choo, Hyunah; Cho, Yong Seo; No, Kyoung Tai; Pae, Ae Nim.
In: Bioorganic and Medicinal Chemistry, Vol. 16, No. 2, 15.01.2008, p. 636-643.Research output: Contribution to journal › Article
TY - JOUR
T1 - Novel GSK-3β inhibitors from sequential virtual screening
AU - Kim, Hye Jung
AU - Choo, Hyunah
AU - Cho, Yong Seo
AU - No, Kyoung Tai
AU - Pae, Ae Nim
PY - 2008/1/15
Y1 - 2008/1/15
N2 - Glycogen synthase kinase-3 (GSK-3β) has been emerging as a key therapeutic target for type-2 diabetics, Alzheimer's disease, cancer, and chronic inflammation. For the purpose of finding biologically active and novel compounds and providing new idea for drug-design, we performed virtual screening using commercially available database. Three-dimensional common feature pharmacophore model was developed by using HipHop program provided in Catalyst software and it was used as a query for screening database. Recursive partitioning (RP) model was developed as a filtering system, which was able to classify active and inactive compounds. Eventually, a sequential virtual screening procedure (SQSP) was conducted by applying the common feature pharmacophore and RP model in succession to discover novel potent GSK-3β inhibitors. The final 56 hit compounds were carefully selected considering predicted docking mode in crystal structures. Subsequent enzyme assay for human GSK-3β protein confirmed that three compounds of these hit compounds exhibit micromolar inhibitory activity. Here, we report novel hit compounds and their binding mode in the active site of GSK-3β crystal structure.
AB - Glycogen synthase kinase-3 (GSK-3β) has been emerging as a key therapeutic target for type-2 diabetics, Alzheimer's disease, cancer, and chronic inflammation. For the purpose of finding biologically active and novel compounds and providing new idea for drug-design, we performed virtual screening using commercially available database. Three-dimensional common feature pharmacophore model was developed by using HipHop program provided in Catalyst software and it was used as a query for screening database. Recursive partitioning (RP) model was developed as a filtering system, which was able to classify active and inactive compounds. Eventually, a sequential virtual screening procedure (SQSP) was conducted by applying the common feature pharmacophore and RP model in succession to discover novel potent GSK-3β inhibitors. The final 56 hit compounds were carefully selected considering predicted docking mode in crystal structures. Subsequent enzyme assay for human GSK-3β protein confirmed that three compounds of these hit compounds exhibit micromolar inhibitory activity. Here, we report novel hit compounds and their binding mode in the active site of GSK-3β crystal structure.
UR - http://www.scopus.com/inward/record.url?scp=38549128330&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=38549128330&partnerID=8YFLogxK
U2 - 10.1016/j.bmc.2007.10.047
DO - 10.1016/j.bmc.2007.10.047
M3 - Article
C2 - 18006321
AN - SCOPUS:38549128330
VL - 16
SP - 636
EP - 643
JO - Bioorganic and Medicinal Chemistry
JF - Bioorganic and Medicinal Chemistry
SN - 0968-0896
IS - 2
ER -