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Anticancer Pyrroloquinazoline LBL1 Targets Nuclear Lamins.

ABSTRACT: Target identification of bioactive compounds is critical for understanding their mechanism of action. We previously discovered a novel pyrroloquinazoline compound LBL1 with significant anticancer activity. However, its molecular targets remain to be established. Herein, we developed a clickable photoaffinity probe based on LBL1. Using extensive chemical, biochemical, and cellular studies with this probe and LBL1, we found that LBL1 targets nuclear lamins, which are type V intermediate filament (IF) proteins. Further studies showed that LBL1 binds to the coiled-coil domain of lamin A. These results revealed that IF proteins can also be targeted with appropriate small molecules besides two other cytoskeletal proteins actin filaments and microtubules, providing a novel avenue to investigate lamin biology and a novel strategy to develop distinct anticancer therapies.

SUBMITTER: Li BX

PROVIDER: S-EPMC6021125 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Anticancer Pyrroloquinazoline LBL1 Targets Nuclear Lamins.

Li Bingbing X BX Chen Jingjin J Chao Bo B David Larry L LL Xiao Xiangshu X

ACS chemical biology 20180419 5

Target identification of bioactive compounds is critical for understanding their mechanism of action. We previously discovered a novel pyrroloquinazoline compound LBL1 with significant anticancer activity. However, its molecular targets remain to be established. Herein, we developed a clickable photoaffinity probe based on LBL1. Using extensive chemical, biochemical, and cellular studies with this probe and LBL1, we found that LBL1 targets nuclear lamins, which are type V intermediate filament ( ...[more]

PMID: 29648791

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