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Updated: Jun 28, 2026

Examining BCL-2 Family Function with Large Unilamellar Vesicles
Published on: October 5, 2012
Structure-activity relationship studies of phenanthridine-based Bcl-XL inhibitors
Paul H Bernardo1, Kah-Fei Wan, Thirunavukkarasu Sivaraman
1Institute of Chemical & Engineering Sciences, Agency for Science Technology and Research (A*STAR), 1 Pesek Road, Jurong Island, Singapore.
Abstract:
Despite their structural similarities, the natural products chelerythrine ( 5) and sanguinarine ( 6) target different binding sites on the pro-survival Bcl-X L protein. This paper details the synthesis of phenanthridine-based analogues of the natural products that were used to probe this difference in binding profiles. The inhibitory constants for these compounds were then measured in a fluorescence polarization assay against Bcl-X L and the tagged Bak-BH3 peptide. The results led to structure-activity relationship studies, which identified the structural motifs required for binding-site specificity as well as inhibitory activity. We also identified synthetic analogues of the natural products that display similar binding modes but with more potent IC 50 values.
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