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:6.2.1.1 (
ACS
)
78,556
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Despite being extensively characterized structurally and biochemically, the functional role of
histone deacetylase 8
(
HDAC8
) has remained largely obscure due in part to a lack of known cellular substrates. Herein, we describe an unbiased approach using chemical tools in conjunction with sophisticated proteomics methods to identify novel non-histone nuclear substrates of
HDAC8
, including the tumor suppressor ARID1A. These newly discovered substrates of
HDAC8
are involved in diverse biological processes including mitosis, transcription, chromatin remodeling, and RNA splicing and may help guide therapeutic strategies that target the function of
HDAC8
.
ACS
Chem Biol 2014 Oct 17
PMID:An unbiased approach to identify endogenous substrates of "histone" deacetylase 8. 2508 60
A novel, isoform-selective inhibitor of
histone deacetylase 8
(
HDAC8
) has been discovered by the repurposing of a diverse compound collection. Medicinal chemistry optimization led to the identification of a highly potent (0.8 nM) and selective inhibitor of
HDAC8
.
ACS
Med Chem Lett 2016 Oct 13
PMID:Development of a Potent and Selective HDAC8 Inhibitor. 2777 31
Schistosomiasis (also known as bilharzia) is a neglected tropical disease caused by platyhelminths of the genus
Schistosoma
. The disease is endemic in tropical and subtropical areas of the world where water is infested by the intermediate parasite host, the snail. More than 800 million people live in endemic areas and more than 200 million are infected and require treatment. Praziquantel (PZQ) is the drug of choice for schistosomiasis treatment and transmission control being safe and very effective against adult worms of all the clinically relevant
Schistosoma
species. Unfortunately, it is ineffective on immature, juvenile worms; therefore, it does not prevent reinfection. Moreover, the risk of development and spread of drug resistance because of the widespread use of a single drug in such a large population represents a serious threat. Therefore, research aimed at identifying novel drugs to be used alone or in combination with PZQ are needed.
Schistosoma mansoni
histone deacetylase 8
(
Sm
HDAC8) is a class I zinc-dependent HDAC, which is abundantly expressed in all stages of its life cycle, thus representing an interesting target for drug discovery. Through virtual screening and phenotypical characterization of selected hits, we discovered two main chemical classes of compounds characterized by the presence of a hydroxamate-based metal binding group coupled to a spiroindoline or a tricyclic thieno[3,2-
b
]indole core as capping groups. Some of the compounds of both classes were deeply investigated and showed to impair viability of larval, juvenile, and adult schistosomes, to impact egg production
in vitro
and/or to induce morphological alterations of the adult schistosome reproductive systems. Noteworthy, all of them inhibit the recombinant form of
Sm
HDAC8 enzyme
in vitro
. Overall, we identified very interesting scaffolds, paving the way to the development of effective antischistosomal agents.
ACS
Infect Dis 2020 01 10
PMID:Screening and Phenotypical Characterization of
Schistosoma mansoni
Histone Deacetylase 8 (
Sm
HDAC8) Inhibitors as Multistage Antischistosomal Agents. 3166 56
