Preferred Label : PRMT5 Inhibitor AZD3470;
NCIt synonyms : MTA Cooperative PRMT5 Inhibitor AZD3470;
NCIt definition : An orally bioavailable second generation methylthioadenosine (MTA)-selective small
molecule inhibitor of the protein arginine methyltransferase 5 (PRMT5), with potential
antineoplastic activity. Upon oral administration, PRMT5 inhibitor AZD3470 inhibits
PRMT5 in the presence of MTA, thereby specifically inhibiting the function of PRMT5
solely within methylthioadenosine phosphoylase (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. 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.;
Molecule name : AZD-3470; AZD 3470;
Origin ID : C203679;
concept_is_in_subset
- has_target
