Abstract:
:Background: Andrographolide and its benzylidene derivatives, SRJ09 and SRJ23, potentially bind oncogenic K-Ras to exert anticancer activity. Their molecular interactions with K-Ras oncoproteins that lead to effective biological activity are of major interest. Methods & results:In silico docking and molecular dynamics simulation were performed using Glide and Desmond, respectively; while saturation transfer difference NMR was performed using GDP-bound K-RasG12V. SRJ23 was found to bind strongly and selectively to K-RasG12V, by anchoring to a binding pocket (namely p2) principally via hydrogen bond and hydrophobic interactions. The saturation transfer difference NMR analysis revealed the proximity of protons of functional moieties in SRJ23 to K-RasG12V, suggesting positive binding. Conclusion: SRJ23 binds strongly and interacts stably with K-RasG12V to exhibit its inhibitory activity.
journal_name
Future Med Chemjournal_title
Future medicinal chemistryauthors
Quah SY,Tan MS,Ho KL,Manan NA,Gorfe AA,Deb PK,Sagineedu SR,Stanslas Jdoi
10.4155/fmc-2020-0104subject
Has Abstractpub_date
2020-09-01 00:00:00pages
1611-1631issue
18eissn
1756-8919issn
1756-8927journal_volume
12pub_type
杂志文章abstract::Computer-aided drug design (CADD) methodologies have made great advances and contributed significantly to the discovery and/or optimization of many clinically used drugs in recent years. CADD tools have likewise been applied to the discovery of inhibitors of HIV-1 integrase, a difficult and worthwhile target for the d...
journal_title:Future medicinal chemistry
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