Preferred Label : LSD1/HDAC6 Inhibitor JBI-802;
NCIt definition : An orally bioavailable inhibitor of two proteins that are part of the corepressor
to the silencer repressor element 1 (RE1) silencing transcription factor (REST) complex
(CoREST complex): histone deacetylase (HDAC) type 6 (HDAC6; HDAC-6) and lysine-specific
demethylase 1 (LSD1; KDM1A), with potential antineoplastic activity. Upon oral administration,
LSD1/HDAC6 inhibitor JBI-802 targets, binds to and inhibits the activity of HDAC6,
and prevents the HDAC6-mediated aggresomal degradation of ubiquitinated proteins.
This results in an accumulation of highly acetylated chromatin histones, the induction
of chromatin remodeling and an altered pattern of gene expression. This results in
a selective transcription of tumor suppressor genes, tumor suppressor protein-mediated
inhibition of tumor cell division and an induction of apoptosis in tumor cells that
overexpress HDAC6. It also modulates genes involved in immune suppression. In addition,
JBI-802 specifically targets, binds to and inhibits LSD1, a demethylase that suppresses
the expression of target genes by converting the di- and mono-methylated forms of
lysine at position 4 of histone 3 (H3K4) to mono- and unmethylated H3K4, respectively.
LSD1 inhibition enhances H3K4 methylation and increases the expression of tumor suppressor
genes. This may lead to an inhibition of cell growth in LSD1-overexpressing tumor
cells. In addition, LSD1 demethylates mono- or di-methylated H3K9 which increases
gene expression of tumor promoting genes; inhibition of LSD1 promotes H3K9 methylation
and decreases transcription of these genes. HDAC6, which is upregulated in many tumor
cell types, deacetylates chromatin histone proteins. LSD1 is overexpressed in a number
of tumor cell types. LSD1 acts on histone H3 as a transcription co-repressor through
demethylation of lysine 4 (H3K4) or as a transcription co-activator through demethylation
of lysine 9 (H3K9).;
Molecule name : JBI-802; JBI 802;
NCI Metathesaurus CUI : CL1792020;
Origin ID : C187112;
UMLS CUI : C5706359;
Semantic type(s)
- concept_is_in_subset
- has_target
