Preferred Label : PRMT5-MTA Inhibitor MRTX1719;
NCIt synonyms : PRMT5-MTA Complex Inhibitor MRTX1719; MTA-cooperative PRMT5 Inhibitor MRTX1719;
NCIt related terms : MRTX-1719;
NCIt definition : An orally bioavailable inhibitor of the protein arginine methyltransferase 5 (PRMT5)-methylthioadenosine
(MTA) complex, with potential antineoplastic activity. Upon oral administration, PRMT5-MTA
inhibitor MRTX1719 selectively binds to the PRMT5-MTA complex that is elevated in
methylthioadenosine phosphoylase (MTAP)-deleted cancer cells, thereby specifically
inhibiting the function of PRMT5 solely within 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 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 cancer cells. MRTX1719 also
causes dysregulated RNA splicing and decreased pRb. Together, this decreases proliferation
and increases apoptosis specifically in MTAP-deleted 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.
Elevated levels are associated with decreased patient survival. MTAP is deleted in
certain cancer cells leading to an accumulation of the metabolite MTA; MTA binds to
and partially inhibits the activity of PRMT5.;
UNII : AY4A8WD6JS;
CAS number : 2630904-44-6;
Molecule name : MRTX 1719; MRTX-1719;
NCI Metathesaurus CUI : CL1779204;
Origin ID : C187048;
UMLS CUI : C5667108;
Semantic type(s)
- concept_is_in_subset
- has_target
