Synthesis and Characterization of a Positron Emission Tomography Imaging Probe Selectively Targeting the Second Bromodomain of Bromodomain Protein BRD4

Two tandem bromodomains (BD1 and BD2) of bromodomain and extraterminal domain (BET) family proteins have shown distinct roles in mediating gene transcription and expression. Inhibitors that interact with a specific bromodomain may contribute to a specific therapeutic potential with fewer side effect...

Full description

Saved in:
Bibliographic Details
Published in:Bioconjugate chemistry 2021-08, Vol.32 (8), p.1711-1718
Main Authors: Bai, Ping, Lan, Yu, Wang, Hao, Liu, Yan, Striar, Robin, Yuan, Gengyang, Afshar, Sepideh, Zagaroli, Julia S, Tocci, Darcy R, Langan, Amelia G, Wang, Changning
Format: Article
Language:English
Subjects:
Emissions
Gene expression
Medical imaging
Organs
Positron emission
Positron emission tomography
Proteins
Side effects
Tomography
Transcription
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Two tandem bromodomains (BD1 and BD2) of bromodomain and extraterminal domain (BET) family proteins have shown distinct roles in mediating gene transcription and expression. Inhibitors that interact with a specific bromodomain may contribute to a specific therapeutic potential with fewer side effects. However, little is known about this disease-related target. Positron emission tomography (PET) imaging could allow us to achieve in-depth knowledge of the BD2 bromodomain. Herein we describe the radiosynthesis and evaluation of [11C]1 as a BRD4 BD2 bromodomain PET imaging radioligand. Our preliminary PET imaging results in rodents demonstrated that [11C]1 had suitable biodistribution in peripheral organs and tissues. Further blocking studies indicated that [11C]1 had good binding specificity toward the BD2 bromodomain. This study may pave the way for the development of a PET radioligand specifically targeting BD1/2 bromodomains as well as for the biological mechanism investigation of BD1/2 bromodomains.
ISSN:1043-1802
1520-4812
DOI:10.1021/acs.bioconjchem.1c00245