E-resources
Peer reviewed
-
Zalloum, Hiba; Tayyem, Rabab; Irmaileh, Basha'er Abu; Bustanji, Yasser; Zihlif, Malek; Mohammad, Mohammad; Rjai, Talal Abu; Mubarak, Mohammad S.
Journal of molecular graphics & modelling, 09/2015, Volume: 61Journal Article
Pharmacophoric features of the binding models Hypo 4/15 and Hypo9/12 (HBD as violet vectored spheres and Hbic as blue spheres, PosIon as red spheres, RingArom as orange vectored spheres, and exclusion volumes as gray spheres), fitted against the most active hit 120 (IC50=1.43 μM, Table 4). Display omitted •Pharmacophoric space of 115 (HER2/ErbB2) inhibitors was explored.•Two pharmacophore models, Hypo4/15 and Hypo9/12, illustrated the best performance.•In silico screening of NCI and DrugBank databases identified 80 potential HER2 inhibitors.•4 of investigated hits selectively inhibited the growth of SKOV3 ovarian cells with IC50<5μM. To discover potential antitumor agents directed toward human epidermal growth factor receptor-2HER2/ErbB2 overexpression in cancer, we have explored the pharmacophoric space of 115 HER2/ErbB2 inhibitors. This identified 240 pharmacophores which were subsequently clustered into 20 groups and cluster centers were used as 3D-pharmacophoric descriptors in QSAR analysis with 2D-physicochemical descriptors to select the optimal combination. We were obliged to use ligand efficiency as the response variable because the logarithmic transformation of bioactivities failed to access self-consistent QSAR models. Two binding pharmacophore models emerged in the optimal QSAR equation, suggesting the existence of distinct binding modes accessible to ligands within the HER2/ErbB2 binding pocket. The QSAR equation and its associated pharmacophore models were employed to screen the National Cancer Institute (NCI) and Drug Bank databases to search for new, promising, and structurally diverse HER2 inhibitory leads. Inhibitory activities were tested against HER2-overexpressing SKOV3 Ovarian cancer cell line and MCF-7 which express low levels of HER2. In silico mining identified 80 inhibitors out of which four HER2 selective compounds inhibited the growth of SKOV3 cells with IC50 values < 5μM and with virtually no effect in MCF-7 cells. These lead compounds are excellent candidates for further optimization.
Shelf entry
Permalink
- URL:
Impact factor
Access to the JCR database is permitted only to users from Slovenia. Your current IP address is not on the list of IP addresses with access permission, and authentication with the relevant AAI accout is required.
Year | Impact factor | Edition | Category | Classification | ||||
---|---|---|---|---|---|---|---|---|
JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
Select the library membership card:
If the library membership card is not in the list,
add a new one.
DRS, in which the journal is indexed
Database name | Field | Year |
---|
Links to authors' personal bibliographies | Links to information on researchers in the SICRIS system |
---|
Source: Personal bibliographies
and: SICRIS
The material is available in full text. If you wish to order the material anyway, click the Continue button.