Preferred Label : Ralometostat;
NCIt synonyms : 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, ralometostat 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.;
UNII : X7CRL5YNN5;
CAS number : 2760481-53-4;
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
