Towards the virtual screening of BIK inhibitors with the homology-modeled protein structure

Induction of apoptosis in tumor cells through direct triggering of the Bcl-2 regulated intrinsic pathway by small molecules carries great potential to overcome the shortcomings of current anticancer therapies. The Bcl-2 family members are crucial regulators of apoptosis. The BIK protein, is an impor...

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Bibliographic Details
Published inMedicinal chemistry research Vol. 22; no. 3; pp. 1184 - 1196
Main Authors Kondagari, Bhargavi, Dulapalli, Ramasree, Krishna Murthy, Dwarkanath, Vuruputuri, Uma
Format Journal Article
LanguageEnglish
Published New York Springer-Verlag 01.03.2013
Subjects
Biochemistry
Biomedical and Life Sciences
Biomedicine
Cell Biology
Original Research
Pharmacology/Toxicology
Virtual screening
ADME
BIK
Glide
Homology modeling
Cancer
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Summary:Induction of apoptosis in tumor cells through direct triggering of the Bcl-2 regulated intrinsic pathway by small molecules carries great potential to overcome the shortcomings of current anticancer therapies. The Bcl-2 family members are crucial regulators of apoptosis. The BIK protein, is an important member of the Bcl-2 family and an attractive drug target. Homology model of BIK was developed based on the crystal structures of appropriate template. We have employed structure-based virtual screening techniques using Glide 5.6 to identify lead like molecules from an in-house library. The database has yielded 345 hits, the top scoring 60 ligands were selected and a pharmacokinetic analysis (ADME) was performed. We have identified six ligands from the combined approach of virtual screening followed by ADME that can work against BIK.
ISSN:1054-2523
1554-8120
DOI:10.1007/s00044-012-0105-z