Anticancer Pyrroloquinazoline LBL1 Targets Nuclear Lamins

Bingbing X. Li, Jingjin Chen, Bo Chao, Larry David, Xiangshu Xiao

Research output: Contribution to journalArticle

4 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1380-1387
Number of pages8
JournalACS Chemical Biology
Volume13
Issue number5
DOIs
StatePublished - May 18 2018

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Lamins
Intermediate Filament Proteins
Lamin Type A
Cytoskeletal Proteins
Actin Cytoskeleton
Microtubules
Actins
Molecules
Therapeutics

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine

Cite this

Anticancer Pyrroloquinazoline LBL1 Targets Nuclear Lamins. / Li, Bingbing X.; Chen, Jingjin; Chao, Bo; David, Larry; Xiao, Xiangshu.

In: ACS Chemical Biology, Vol. 13, No. 5, 18.05.2018, p. 1380-1387.

Research output: Contribution to journalArticle

Li, Bingbing X. ; Chen, Jingjin ; Chao, Bo ; David, Larry ; Xiao, Xiangshu. / Anticancer Pyrroloquinazoline LBL1 Targets Nuclear Lamins. In: ACS Chemical Biology. 2018 ; Vol. 13, No. 5. pp. 1380-1387.
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