You are here

J Med Chem DOI:10.1021/jm500872p

In vivo imaging of histone deacetylases (HDACs) in the central nervous system and major peripheral organs.

Publication TypeJournal Article
Year of Publication2014
AuthorsWang, C, Schroeder, FA, Wey, H-Y, Borra, R, Wagner, FF, Reis, S, Kim, SWon, Holson, EB, Haggarty, SJ, Hooker, JM
JournalJ Med Chem
Volume57
Issue19
Pages7999-8009
Date Published2014 Oct 09
ISSN1520-4804
KeywordsAnimals, Autoradiography, Brain, Dose-Response Relationship, Drug, Epigenomics, Histone Deacetylase Inhibitors, Histone Deacetylases, Humans, Kidney, Male, Myocardium, Papio, Positron-Emission Tomography, Rats, Rats, Sprague-Dawley
Abstract

Epigenetic enzymes are now targeted to treat the underlying gene expression dysregulation that contribute to disease pathogenesis. Histone deacetylases (HDACs) have shown broad potential in treatments against cancer and emerging data supports their targeting in the context of cardiovascular disease and central nervous system dysfunction. Development of a molecular agent for non-invasive imaging to elucidate the distribution and functional roles of HDACs in humans will accelerate medical research and drug discovery in this domain. Herein, we describe the synthesis and validation of an HDAC imaging agent, [(11)C]6. Our imaging results demonstrate that this probe has high specificity, good selectivity, and appropriate kinetics and distribution for imaging HDACs in the brain, heart, kidney, pancreas, and spleen. Our findings support the translational potential for [(11)C]6 for human epigenetic imaging.

DOI10.1021/jm500872p
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/25203558?dopt=Abstract

Alternate JournalJ. Med. Chem.
PubMed ID25203558
PubMed Central IDPMC4191584
Grant ListS10RR022976 / RR / NCRR NIH HHS / United States
R01DA028301 / DA / NIDA NIH HHS / United States
S10 RR022976 / RR / NCRR NIH HHS / United States
R01DA030321 / DA / NIDA NIH HHS / United States
S10RR026666 / RR / NCRR NIH HHS / United States
R01 DA030321 / DA / NIDA NIH HHS / United States
S10 RR029495 / RR / NCRR NIH HHS / United States
S10RR019933 / RR / NCRR NIH HHS / United States
S10 RR017208 / RR / NCRR NIH HHS / United States
P41EB015896 / EB / NIBIB NIH HHS / United States
S10 RR026666 / RR / NCRR NIH HHS / United States
K99 DA037928 / DA / NIDA NIH HHS / United States
S10 RR023385 / RR / NCRR NIH HHS / United States
S10RR017208 / RR / NCRR NIH HHS / United States
S10RR029495 / RR / NCRR NIH HHS / United States
R01 DA028301 / DA / NIDA NIH HHS / United States
S10 RR019933 / RR / NCRR NIH HHS / United States
P41 EB015896 / EB / NIBIB NIH HHS / United States