TY - JOUR
T1 - Anticancer Pyrroloquinazoline LBL1 Targets Nuclear Lamins
AU - Li, Bingbing X.
AU - Chen, Jingjin
AU - Chao, Bo
AU - David, Larry L.
AU - Xiao, Xiangshu
N1 - Publisher Copyright:
© 2018 American Chemical Society.
PY - 2018/5/18
Y1 - 2018/5/18
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85047458306&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85047458306&partnerID=8YFLogxK
U2 - 10.1021/acschembio.8b00266
DO - 10.1021/acschembio.8b00266
M3 - Article
C2 - 29648791
AN - SCOPUS:85047458306
SN - 1554-8929
VL - 13
SP - 1380
EP - 1387
JO - ACS chemical biology
JF - ACS chemical biology
IS - 5
ER -