Preferred Label : PRMT5 Inhibitor TNG456;
NCIt synonyms : MTA Cooperative PRMT5 Inhibitor TNG456; MTA-cooperative PRMT5 Inhibitor TNG456; Protein Arginine Methyltransferase 5 Inhibitor TNG456;
NCIt definition : An orally bioavailable, blood-brain-barrier (BBB) penetrant and methylthioadenosine
(MTA)-selective inhibitor of the protein arginine methyltransferase 5 (PRMT5), with
potential antineoplastic activity. Upon oral administration, PRMT5 inhibitor TNG456
targets, binds to and inhibits PRMT5 that is bound to MTA, thereby specifically inhibiting
the function of PRMT5 solely within methylthioadenosine phosphorylase (MTAP)-deleted
cancer cells and not in normal, healthy cells. By inhibiting the methyltransferase
activity of PRMT5, levels of both monomethylated and dimethylated arginine residues
in certain histones and non-histone proteins are decreased. This modulates the expression
of genes involved in several cellular processes and may increase the expression of
antiproliferative genes and/or decrease the expression of genes that promote cell
proliferation. This may lead to decreased growth of rapidly proliferating cancer cells.
PRMT5, a type II methyltransferase that catalyzes the formation of both omega-N monomethylarginine
(MMA) and symmetric dimethylarginine (sDMA) on histones and a variety of other protein
substrates involved in signal transduction and cellular transcription, is essential
for the viability of cancer and normal cells. It is overexpressed in several neoplasms
and elevated levels are associated with decreased patient survival. MTAP is deleted
in certain cancer cells leading to an accumulation of the metabolite MTA. As MTA binds
to and inhibits the activity of PRMT5, MTAP-deficient cancer cells are specifically
sensitive to PRMT5 inhibitors.;
Molecule name : TNG 456; TNG-456;
Origin ID : C215699;
concept_is_in_subset
- has_target
