Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.6.3.44 (
P-glycoprotein
)
13,344
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Histone deacetylase 6
(
HDAC6
) is a unique member of the HDAC family because of its characteristics, namely, its cytoplasmic localization and ubiquitin binding.
HDAC6
has been implicated in cancer metastasis and neurodegeneration. In the present study, we performed radiosynthesis and biological evaluation of a fluorine-18-labeled ligand [
18
F]3, which is an analog of the
HDAC6
-selective inhibitor tubastatin A, for positron emission tomography (PET) imaging. [
18
F]3 was synthesized by a two-step reaction composed of
18
F-fluorination and formation of a hydroxamic acid group. IC
50
values of 3 against HDAC1 and
HDAC6
activities were 996 nM and 33.1 nM, respectively. A biodistribution study in mice demonstrated low brain uptake of [
18
F]3. Furthermore, bone radioactivity was stable at around 2% ID/g after injection, suggesting high tolerance to defluorination. Regarding metabolic stability, 70% of the compound was observed as the unchanged form at 30 minutes post injection in mouse plasma. A small animal PET study in mice showed that pretreatment with cyclosporine A had no effect on initial brain uptake of [
18
F]3, suggesting low brain uptake of [
18
F]3 was not caused by the
P-glycoprotein
-mediated efflux. While PET imaging using [
18
F]3 has a limitation with respect to neurodegenerative diseases, further studies evaluating its utility for certain cancers are worth evaluating.
...
PMID:Radiosynthesis and preliminary evaluation of an
18
F-labeled tubastatin A analog for PET imaging of histone deacetylase 6. 3188 Nov 7
