Preferred Label : PRMT5 Inhibitor TNG908;
NCIt definition : An orally available small molecule inhibitor of protein arginine methyltransferase
5 (PRMT5), with potential antiproliferative and antineoplastic activities. Upon oral
administration, PRMT5 inhibitor TNG908 selectively binds to PRMT5 and inhibits its
function. By inhibiting its methyltransferase activity, levels of both monomethylated
and dimethylated arginine residues in histones H2A, H3 and H4 are decreased. This
modulates the expression of genes involved in several cellular processes, including
cellular proliferation. This may increase the expression of antiproliferative genes
and/or decrease the expression of genes that promote cell proliferation, which may
lead to decreased growth of rapidly proliferating cells, including 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 overexpressed
in several neoplasms and is essential for the viability of cancer and normal cells.
Elevated levels are associated with decreased patient survival. Methylthioadenosine
phosphorylase (MTAP) is deleted in certain cancer cells leading to an accumulation
of methylthioadenosine (MTA). As MTA binds to and partially inhibits PRMT5, MTAP-null
cancer cells are specifically sensitive to PRMT5 inhibitors. This may spare normal,
healthy cells that are without MTAP-deletions and lower systemic toxicity.;
Molecule name : TNG-908; TNG 908;
NCI Metathesaurus CUI : CL1792027;
Origin ID : C187119;
UMLS CUI : C5706366;
Semantic type(s)
- concept_is_in_subset
- has_target
